Recent developments in neuroanatomic, lesion and stimulation, and functional brain mapping studies offer great promise in the search for the neural substrates of anxiety. Animal studies have provided important clues about the neural pathways that underlie certain aspects of the evaluative and expressive components of anxiety. As a brain-imaging technique that safely permits the study of the living human brain, positron emission tomography is likely to provide additional information about the neural structures that underlie the evaluation, expression, and experience of anxiety in each of its normal and pathologic forms. The quest to establish the neural substrates of anxiety has two parts: identification of the elementary psychophysiologic operations that define anxiety and identification of the precise neural pathways that underlie each of these operations. To paraphrase an investigator who is involved in this quest, the challenge and charm of this field are that studies of both the mind and the brain are required.