Suicidal behavior is the result of a combination of factors that span the domains of psychopathology, genetics, early life experience, family interactions, social stress, physical illness, and neurobiology. To develop predictive and explanatory models of suicidal behavior it is necessary to consider all of these domains. A stress-diathesis model is proposed that classifies risk factors for suicidal behavior into those that are trait-dependent and those that are state-dependent. The timing of suicidal behavior is determined by state-dependent factors. The relationship of psychopathologic factors such as severity of depression or anxiety to suicide will be discussed. Biologic changes that correlate with suicide may be either state- or trait-dependent. Particular emphasis will be given to changes in the serotonin system and how these may represent a constitutional risk factor as opposed to a state-dependent risk factor for suicidal behavior.