For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and adolescence, including the overproduction and selective elimination of synapses, is based on genetic programming and experience. The effects of stimulant drugs during different stages of this process have unique short-term, acute effects that also influence their long-term effects. Chronic, pre-pubertal exposure alters the expected developmental trajectory of brain structure and function and results in a different topography in adulthood. The timing of exposure (childhood versus adolescence), the age of examination after drug exposure (immediately or delayed into adulthood) and sex influence the observable effects. Preclinical studies of the effects of stimulant exposure provide increased understanding about the impact of stimulant drugs on brain development and provide insight into new treatment options for ADHD and other disorders of childhood.