The future harbours the potential for myriad threats to the fitness of organisms, and many species prepare accordingly based on indicators of hazards. Here, we distinguish between defensive responses on the basis of sensed cues and those based on autocues generated by mental simulations of the future in humans. Whereas sensed threat cues usually induce specific responses with reference to particular features of the environment or generalized responses to protect against diffuse threats, autocues generated by mental simulations of the future enable strategic preparation for hazards that may not require an immediate response. The overlap of these mechanisms makes defence effective and versatile, yet can manifest as contemporary anxiety disorders in humans.