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Commas are tricky. There are firm rules about commas, there are squishy rules about commas, there are style variations with commas, there are international differences in comma usage, and then there’s the fact that you can play with them and develop your own special comma flair, and no one can stop you.
Even worse, it’s terribly difficult to talk about commas without getting into grammar terminology, and most people would rather stick their heads in an oven than talk about gerunds. (I promise not to make you talk about gerunds. Today.)
All of which may lead the intrepid comma user to throw up her hands and say, “I can’t sort all this out. There are no firm comma guidelines. I will just stick them in whenever there should be a pause in the sentence.”
Please don’t do that. It makes my heart hurt. There are in fact some hard-and-fast rules for comma usage, and they are worth knowing. Once you know them–and I mean really know them, like in-your-bones know them–then you can start mastering all the intricacies of comma style and comma freedoms and whatnot. But first you really ought to have some idea what you’re doing when you punctuate.
So what I’m going to do is start with what I consider to be Comma Rule Numero Uno:

If you have two independent clauses joined by a conjunction, you must separate them with a comma.

If you’re nodding your head, you probably don’t need to read this post. But if that sentence sounds like gibberish to you, carry on, because the world would truly be a better place if every writer understood Comma Rule Numero Uno.
 
So. First. What the hell is a clause?
Well, a clause is a group of words that contains a subject and a predicate. (You hate me now, don’t you?) Think “doer” for “subject” and “thing they’re doing” for “predicate.” Think “noun” and “verb.” You can totally handle this.
Let’s have a look at some clauses. We’ll make them erotic, just for kicks.

  • Cath gasped
  • When he stroked her thigh
  • She cried “yes”

All different, all clauses.
Taking them one at a time:

  • Cath gasped: This one is simple. Cath is the subject (Who did it?), and gasped is the predicate (What did she do?). Cath is the noun, and gasped is the verb.
  • When he stroked her thigh: The subject is he, because he is the one with the magic thigh-stroking fingers. The predicate is stroked her thigh, because thigh-stroking is what he’s all about. Or, looked at slightly differently, the noun/verb combination is he stroked. (The object is thigh. Her is functioning as an adjective that modifies thigh.)
  • She cried “yes”: Here, she is the subject (Who did it?), and cried yes is the predicate (What did she do?). She is the noun, and cried is the verb. (“Yes” is the object.)

Still with me? Okay. So, those are three clauses, but only two of them are independent clauses. An independent clause can stand alone as a sentence. Cath gasped and She cried “yes” are both independent clauses.
A dependent clause has to be stuck onto something else to make a proper sentence. When he stroked her thigh is a dependent clause. It’s not a complete thought. It’s only a sort of half-thought, leaving you wondering, “What? What did she do when he stroked her thigh? Tell me, for the love of God.”
You don’t need to worry about dependent clauses for the remainder of this post. They are dead to you.
 
Focus on the independent clauses, and look back at Comma Rule Numero Uno: If you have two independent clauses joined by a conjunction, you must separate them with a comma.
Conjunctions are easy: they are the glue we use to stick sentences together. In English, there aren’t all that many. They are words like and, but, for, nor, so, or, because, though, and yet. (There are probably others, but these are the ones we tend to use the most.)
 
Let’s make a sentence, shall we?

  • Cath gasped, and she cried, “Yes!”

Independent clause. Comma. Conjunction. Second independent clause. Perfection.
Now let’s make a not-sentence:

  • Cath gasped and she cried, “Yes!”

That, my dears, is a run-on: a sad excuse for a sentence that joins two independent clauses without a comma.
This is also a not-sentence:

  • Cath gasped, she cried, “Yes!”

It’s what is known as a comma splice: a sentence that uses a comma without a conjunction to join two independent clauses. Big no-no.
 
Let’s look at some more, just to make sure the picture is clear:

  • The train wouldn’t depart for a few minutes yet, and there were still seats available.
  • Cath peered at him suspiciously, worrying the victory had come far too easily, but he remained still, and after a while she started to feel rude for staring.
  • She couldn’t seem to find a pen, though she pawed around in her bag for ages.
  • Cath cast her eyes heavenward in an attempt to keep up a good front, but really, how was she supposed to resist a man who came courting with junk food?
  • She tried to let that slide, but it slid down between her breasts, wriggled over her belly, and warmed up the junction of her thighs.

Each one of these sentences contains two independent clauses joined with a comma and a conjunction. (Some of them are tricky and contain other stuff as well, but try to filter out the filler words and home in on the subject/predicate combinations.) See if you can find them. I’ll wait.
 
Lacking either the comma or the conjunction, all of those sentences become not-sentences:

  • The train wouldn’t depart for a few minutes yet and there were still seats available. Run-on.
  • The train wouldn’t depart for a few minutes yet, there were still seats available. Comma splice.
  • Cath peered at him suspiciously, worrying the victory had come far too easily but he remained still, and after a while she started to feel rude for staring. Run-on.
  • Cath peered at him suspiciously, worrying the victory had come far too easily, he remained still, and after a while she started to feel rude for staring. Comma splice.
  • She couldn’t seem to find a pen though she pawed around for ages. Run-on.
  • She couldn’t seem to find a pen, she pawed around for ages. Comma splice.

You get the idea.
 
But what if you don’t want to join your independent clauses with a comma? What, pray tell, are your other options?
Here’s where our good friend the semicolon comes in handy. Semicolons can join two independent clauses without a conjunction. Thus, all of these are permissible:

  • The train wouldn’t depart for a few minutes yet; there were still seats available.
  • Cath peered at him suspiciously, worrying the victory had come far too easily; he remained still, and after a while she started to feel rude for staring.
  • She couldn’t seem to find a pen; she pawed around for ages.

All technically correct. However, semicolons work best with two independent clauses that are closely linked conceptually. Also, semicolons don’t pop up all that much in fiction, I suspect because they’re formal enough to catch the reader’s eye. The only one of those last three examples that’s any good as a sentence, I would argue, is the last one. For the other two, you’d be better off just breaking the independent clauses apart into two solitary sentences:

  • The train wouldn’t depart for a few minutes yet. There were still seats available.
  • Cath peered at him suspiciously, worrying the victory had come far too easily. He remained still, and after a while she started to feel rude for staring.

 
When it comes to writing fiction, of course, there are no rules. Authors write run-on sentences all the time. They comma-splice up a storm, giggling maniacally, and nobody stops them. There’s not a thing wrong with that. But when it comes to grammar, knowledge is power. It’s one thing to break the rules deliberately because you want your sentence to have a certain rhythm, and it’s quite another to write run-ons and comma splices because you just don’t know any better. The thing is, even readers who don’t know a comma splice from a barred owl can tell when the author’s grammar sucks, because they’ll trip over your sentences. They’ll misread you. They’ll get irritated with you and put your book aside. And that’s the last thing you want to have happen.
 
Questions? I’ll answer whatever you like in the comments.