This chapter focuses on drug development for psychiatric as opposed to other central nervous system (CNS) indications such as neurological conditions, pain, and sleep. It provides an overview of how CNS drug development has evolved over its relatively short history of perhaps 50-100 years as well as to provide some sense of how it might evolve in the not-too-distant future. Chlorpromazine and other phenothiazine molecules were synthesized around the turn of the last century and some were initially used to treat pinworm infestation. However, chlorpromazine over the last 50 years has come to play a pivotal role in the modern era of clinical psychopharmacology. CNS drug development principally focused on serotonin selective reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors SNRIs, atypical antipsychotics, and cholinesterase inhibitors. The current development of drugs for Alzheimer's and other neurodegenerative diseases could be a model for how future CNS drug development might proceed.