During the quest "Find the Buggy Parts" in the Wasted Garage, the player will encounter the Wasted Boss when nearing the end. This boss is relatively easy to kill, although he is mounted on a vehicle turret. It is advised that you use fatboys to kill him when while he pauses shooting. Additionally, HE Grenades may prove effective.
The second boss is seen in Dead City during the quest "Defibrillator Upgrade". It is the massive mutant scene toward the end of the quest, mentioned by Norbu and After the Impact's lore. The player is given a Rocket Launcher and unlimited HE rockets to defeat him. You then must shoot the highlighted spots on the mutant's body when he reveals them. After killing him, you simply walk down the steps and through the door.
The third boss is seen in the Power Plant. He is the Boss of the Gearheads that continually taunts the player via the intercom, and is found at the end of the quest "The Price of Power". He uses a Combat Shotgun and will attempt to kill the player. He can be quickly killed with the use of pop rockets or HE rockets. After killing him the player then may proceed with the quest.
Towards the end of the quest "Rite of Passage", the player will encounter a warship known as Firestorm. The player then must use the rocket launcher to destroy the warship before it kills the player, or worse, leaves. This is likely the hardest boss in the game as it is faced along with other Scorchers. The player must fire at the warships sides until the blue is visible.You then must continue firing at the sides. Finally, you must target the six blue thrusters until the Warship finally collapses. The player then may use the elevator to find Sarah.