Advances in the conceptualization and measurement of life stress in the past 2 decades raise several questions concerning traditional diathesis-stress theories of psychopathology. First, comprehensive measures of life stress force investigators to become more precise about the particular stressful circumstances hypothesized to interact with diatheses. Second, the influence of the diathesis on a person's life is typically ignored, which results in several types of possible bias in the assessment of life stress. Finally, information is available on diatheses and stress for specific disorders to provide a foundation for more empirically based hypotheses about diathesis-stress interactions. This possibility is outlined for depression. Such an approach provides the basis for developing broader, yet more specific, frameworks for investigating diathesis-stress theories of psychopathology in general and of depression in particular.