“Learned helplessness” refers to debilitating outcomes, such as passivity and increased fear, that follow an uncontrollable adverse event, but do not when that event is controllable. The original explanation argued that when events are uncontrollable the animal learns that outcomes are independent of its behavior, and that this is the active ingredient in producing the effects. Controllable adverse events, in contrast, fail to produce these outcomes because they lack the active uncontrollability element. Recent work on the neural basis of helplessness, however, takes the opposite view. Prolonged exposure to aversive stimulationper seproduces the debilitation by potent activation of serotonergic neurons in the brainstem dorsal raphe nucleus. Debilitation is prevented with an instrumental controlling response, which activates prefrontal circuitry detecting control and subsequently blunting the dorsal raphe nucleus response. Furthermore, learning control alters the prefrontal response to future adverse events, thereby preventing debilitation and producing long-term resiliency. The general implications of these neuroscience findings may apply to psychological therapy and prevention, in particular by suggesting the importance of cognitions and control, rather than habits of control.