In the human, disease or trauma affecting more than a discrete portion of the prefrontal cortex of either the right or left hemisphere generally induces disorders in motility, cognition, emotion, and social behavior. The nature of the disorder varies depending on the location and extent of the damage, although commonly more than one prefrontal region is affected. Dorsolateral damage leads to deficits in attention, planning, working memory, and decision-making. Depression and planning defects are especially common in frontopolar damage. Orbital and medial damage commonly leads to hyperactivity, distractibility, difficulty concentrating, risk-taking behavior, impulsivity, poor error prediction, and antisocial or unethical behavior. Normal aging, probably in conjunction with collateral impoverishment of prefrontal gray matter and connectivity, leads to a gradual deterioration of cognitive functions. That deterioration is precipitous and profound in frontotemporal dementia and Alzheimer’s disease.