In manual mode, you set both the aperture and shutter speed. Decide whether the most important element is depth of field or shutter speed. If you want to control depth of field, set aperture first. If you want to control movement in a shot, set shutter speed first.
You can then adjust the other setting until the index mark is in the middle of the exposure level indicator for a standard exposure. You may also need to increase/decrease ISO to achieve your desired aperture/shutter speed combination.
When using a flashgun or studio lights, Manual mode gives you free reign to set the optimum shutter speed, aperture and ISO for the shot (such as 1/200 sec, f/11, ISO100); you then adjust the output of the flash for your desired exposure.