Rates of prescriptions for very young children have increased notably in the last 20 years. These changes have occurred in the context of increasing attention to early childhood mental health, availability of medications perceived to be safer than older medications, application of the medical model to the mental health care of young children, as well as other cultural shifts. Psychopharmacological treatment for any patient, but especially very young children, requires consideration of central nervous system (CNS) and metabolic development and issues of diagnostic validity and should be guided by an empirical literature. In young children, this literature is quite limited. In this article, the authors review developmental issues involved in psychopharmacological treatment and present existing literature and practical guidelines for common preschool diagnoses, recognizing that for some disorders, the extant literature does not support even consideration of medications.