There are a number of biological theories of panic disorder that figure prominently in the psychiatric literature; we summarize the evidence for or against some of the most promising ones. Certain agents have a powerful and specific capacity to induce panic, in contrast to other agents that produce prominent physiological changes but fail to induce panic. These findings argue strongly against the notion that panic is a reaction to nonspecific distressing stimuli and suggest more specific biological bases, even if these involve multiple neurochemicals and circuits. The various theories described in the following sections should not be viewed as mutually exclusive but rather as potentially interlocking pieces of a larger puzzle. The theories are summarized in Table 12–4; neurochemical, imaging, and genetic findings are described in the discussions that follow.