In many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia, symptoms are present that appear to reflect an essential absence of normal movement, cognition and emotional states. These negative symptoms might reflect fundamental impairments in basic brain mechanisms that underlie goal-directed behaviour. Knowledge of the pathology and pathophysiology of these diseases, combined with evidence from basic science, offers opportunities for understanding the neurobiological basis of goal-directed behaviour, particularly the interaction between limbic structures and striato-thalamo-cortical circuits. The study of patients with negative symptoms also provides opportunities for testing cognitive models of goal-directed behaviour, and eventually to map such models onto the neurobiology of both normal and abnormal behaviour.