For much of Resident Evil 4, Ashley will be by Leon's side - his job is to protect her, after all. However, being a university student, Ashley is not trained in combat and is useless in battle. Therefore, she must be called to "wait here" while Leon advances, or "hide" in nearby crates until Leon whistles to signal the all-clear. If Ashley is grabbed by a Ganado, he will take her to the nearest door. If she is taken out of the area, you will lose the game. You must, therefore, take priority in killing the Ganados near Ashley. Should she be captured, shoot the Ganados in the legs - you cannot risk hitting Ashley, as any hits from gunfire or knife-slashes will lead to an instant death and game over.
While wearing her second alternate costume, unlocked after beating Separate Ways, Ashley is unkillable due to the armor she wears, not a single attack can hurt her (including explosions). Also, when Ganados attempt to kidnap her, they will fall over due to the weight of the armor. Instead of ducking when Leon aims in her direction, Ashley simply lowers her visor. Unfortunately, this can be a hinderance as Ashley can often block Leon's shots.
In Chapter 3-4, Ashley will be controlled by the player as she navigates the castle in search of Leon. There are no firearms or knives to be equipped and used, however, so Ashley must largely run away from the robed cultists. Oddly enough, these enemies won't try to capture Ashley immediately as they do when she is with Leon. Instead, they will try to strangle her until she is unconscious before capturing her (evident by the "game over" screen, they carry her on their shoulder rather than leave her on the ground). The Armaduras encountered later, however, will simply try to kill her with their axes.
In the first two rooms, Ashley can defend herself by throwing explosive lanterns at nearby cultists to kill them. If she runs out of lanterns before defeating them, you must leave the area and return in order to trigger a respawn.
Interestingly, Ashley can suplex cultists if she hits them when opening a door. This only happens in the GameCube version.