Abstract: Defenses, such as flight, cough, stress, and anxiety, should theoretically be expressed to a degree that is near the optimum needed to protect against a given threat. Many defenses seem, however, to be expressed too readily or too intensely. Furthermore, there are remarkably few untoward effects from using drugs to dampen defensive responses. A signal detection analysis of defense regulation can help to resolve this apparent paradox. When the cost of expressing an all-or-none defense is low compared to the potential harm it protects against, the optimal system will express many false alarms. Defenses with graded responses are expressed to the optimal degree when the marginal cost equals the marginal benefit, a point that may vary considerably from the intuitive optimum. Models based on these principles show that the overresponsiveness of many defenses is only apparent, but they also suggest that, in specific instances, defenses can often be dampened without compromising fitness. The smoke detector principle is an essential foundation for making decisions about when drugs can be used safely to relieve suffering and block defenses.