Start with command + shift + 4 to get the crosshairs you can drag over an area of your screen. Release, and you'll find the resulting screen shot file sitting on your desktop.
Next, add control to the above shortcut (control + command + shift + 4) and you'll get the same set of crosshairs, only this time the resulting screen shot will be added to the clipboard, so you can easily paste it into an email, Word document, Photoshop or Illustrator file.
Finally, to get really fancy, hold down the spacebar after using either of the above keyboard shortcuts while you are dragging the cursor to move your screenshot crop area around your screen so you can get your positioning just right before releasing to take the shot. (Works in OS 10.5 and higher - Leopard and Snow Leopard.)