This chapter discusses the effects of coffee consumption on anxiety response, taking into account vulnerability factors such as sex and genetics. In light of research concerning the effects of coffee on normal anxiety, and particularly research carried out in our laboratory, current knowledge can be summarized as follows: (1) men appear to be more sensitive to the effects of coffee than women; and (2) coffee can increase alertness in habitual consumers after acute deprivation, but not above the level of that observed in nonconsumers. In addition, we discuss clinical evidence of the varying sensitivity of anxiety disorder patients to the effects of coffee. The caffeine challenge test, a useful biological model of panic attacks, has shown that individuals suffering panic disorder or performance social anxiety disorder are particularly sensitive to the effects of caffeine and may benefit from a reduction in their intake. This greater sensitivity seems to have a genetic basis.