A variety of personality characteristics predict important health outcomes, such as longevity and the development and course of specific major diseases. The most well-established of these risk factors include hostile or antagonistic interpersonal behavior and negative emotionality. Positive emotionality, conscientiousness, and optimism predict better health outcomes. These prospective associations likely reflect the intervening mechanisms of health behavior and multiple sources and aspects of physiological stress responses. Strengthening the evidence regarding personality and health requires several ongoing and future efforts, including replication of prospective associations using more current and compelling personality assessments, integration of the many traits usually studied in isolation, a similar integration of personality with risk factors that are aspects of social relationships, and formal tests of mediating mechanisms. Such efforts could facilitate the development of interventions intended to prevent and manage illness, by focusing on personality-related risk and resilience.