People's enduring psychological tendencies are reflected in their traits. Contemporary research on personality establishes that traits are rooted largely in biology, and that the central aspects of personality can be captured in frameworks, or taxonomies, focused on five trait dimensions: openness to experience, conscientiousness, extraversion, agreeableness, and emotional stability. In this article, we integrate a five-factor view of trait structure within a holistic model of the antecedents of political behavior, one that accounts not only for personality, but also for other factors, including biological and environmental influences. This approach permits attention to the complex processes that likely underlie trait effects, and especially to possible trait–situation interactions. Primary tests of our hypotheses draw on data from a 2006 U.S. survey, with supplemental tests introducing data from Uruguay and Venezuela. Empirical analyses not only provide evidence of the value of research on personality and politics, but also signal some of the hurdles that must be overcome for inquiry in this area to be most fruitful.