Good question. These terms are thrown around a lot in the printing and graphics world, and it's important to understand the difference.

CMYK (Cyan, Magenta, Yellow, and "Key," or black) are the ink colors used during the printing process. The term "key" is used instead of "black" because, really, this is a mixture of the cyan, magenta, and yellow inks — the resulting "black" can be minutely different from one printing company to another.
RGB (Red, Green, and Blue) are the colors of light used by your monitor to display your document on-screen. Black is not listed because on-screen black is an absence of light. A mixture of red, green, and blue light produces white.

How does this affect me?
Any image you create on your computer should be created in CMYK mode. This will ensure that the colors you see on-screen will most closely match the final printed product. If you create your document in RGB, the colors in your printed product may vary slightly: many of the bright values produced by your monitor cannot be exactly reproduced in print.

A lot of digital images are JPEG files, and JPEGs are almost always in RGB.

Note: Printers, regardless of their type, are unable to print in RGB.

How can I learn more?
If you want to learn more about CMYK and RGB, check out this video from 99designs on the topic:

Skip to a specific topic in the video by following these quick references:

Chapters:

00:00 - RGB vs CMYK: What's the difference?

00:51 - What is RGB?

01:46 - When do you use RGB?

02:13 - What is CMYK?

03:03 - When do you use CMYK?

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