The Spirit Bomb (Genki-Dama) was Goku's most powerful attack, taught to him by King Kai, and only usable by those with a pure heart. To use it, Goku must hold his hands upward and concentrate, calling on nature and all the good beings within a certain range- be they on Earth, in the solar system or within the galaxy- to donate a small portion of their life force. The gathered energy coalesces into a bright, white glowing sphere- the more energy is gathered, the larger it is. The sphere is then pushed at the target, and explodes upon landing (although it can be delayed, if not stopped). As a force of pure good energy, the Spirit Bomb is one of Goku's most effective attacks, but the length of time required to empower it makes it a last resort.
Goku first used the Spirit Bomb on Vegeta (during which the energy had to be passed to Krillin to attack with), then on Frieza (hurting but not killing him), and finally on Majin Buu (destroying him permanently after a great deal of effort).
The Spirit Bomb was also used several times in the films. In the Dragon Ball Z: Budokai video games, Cell can use the Spirit Bomb; however, considering his villainy, this is unlikely to be canon.