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What is the difference between RGB and CMYK?

Different media have different ways of generating colors. The two basic approaches are RGB and CMYK color models. RGB is used mainly in displays while CMYK is used in printing, each specialized to the media they use.
RGB (Red, Green, Blue) is an additive color mode. It is called additive because the background of screen is black. The individual "dots" (today generally individual LEDs) then light up in varying intensity adding light to black. The variations in intensity of each color determines what color the user sees. CMYK (Cyan, Magenta, Yellow, Key or blacK) is subtractive because the paper where its printed on is white and the ink subtracts from the brightness of the white paper.
In short, RGB is used to create images in screens and display, while CMYK is used in printing to paper or other media. Due to their nature RGB has a larger range of colors (or gamut) than CMYK. 
So, if you like to design something to be printed, design it using CMYK, otherwise the colors will look different when printed from what you see on the screen. If you design something to be only used on a screen or display design it in RGB.