Brutal is the hardest difficulty, surpassing Crushing, because Nathan Drake has half as much health, meaning that he can die within 1-3 shots, and he deals half as much damage to enemies. The enemies are much more smarter than ever before, as they have nearly perfect aim, and they deal quadruple damage to Drake. Also, enemies do not drop stealth-killed weapons when stealth-killed. Tweaks and the ability to grant weapons at any is disabled.
Just like Crushing, combat tutorials and some button prompts are disabled. Also, ammo pick-ups never give more than 5 clips of ammo per pick up, making ammo extremely hard to find, thus forcing the player to make every shot count.
Completing the game on Brutal is not required for any of the platinum trophies in the collection, but certain rewards only become available after it's been completed, such as Eddy's Golden Gun in Uncharted: Drake's Fortune and Uncharted 2: Among Thieves, and the Golden AK-47 and 92FS-9mm in all three games.