The aim of the study was to evaluate the use of imaging in the development of neuropharmacological drugs. All New Drug Applications (NDAs) approved from 1995 through 2004 in the Division of Neuropharmacological Drug Products at the Food and Drug Administration were surveyed for imaging studies. Imaging literature was also reviewed with respect to antipsychotics and antidepressants. One hundred and six NDAs (35 new molecular entities (NMEs)) were approved; 15 of these NDAs (10 NMEs) had imaging studies. The primary imaging modality was positron emission tomography. Imaging was primarily conducted for drugs used in schizophrenia, depression, multiple sclerosis, and migraine. The majority evaluated receptor occupancy or proof of concept. Examples (including literature) are discussed as pertinent to dosage, efficacy, safety, or further development of a drug or class of drugs. Imaging contributes to optimal clinical development of central nervous system (CNS)-active drugs. Opportunities are available for its broader use, contributing to improved understanding of the clinical pharmacology of CNS-active drugs.