The Conscientiousness (C) of the self and significant others influences health by way of mediational chains involving socioeconomic attainment, the avoidance and neutralization of stressors, the promotion of health behaviors and the minimization of risk behaviors, and the management of symptoms and diseases. Yet, meta-analyses reveal that these associations are moderated by factors that are not well understood. We propose the Life Course of Personality Model (LCP Model), which comprises a series of hypotheses that suggest how such mediational chains are subject to 2 sources of contingency. First, the mechanisms by which C translates into health and the avoidance of risk change from early childhood to late adulthood, involving processes that are specific to phases of the life course; also, however, C influences health by way of continuous processes extending over many decades of life. Second, C may be more consequential in some social contexts than in others, and when accompanied by some constellations of personality characteristics than by others. That is, the mediational processes by which C translates into health and the avoidance of disease are likely moderated by timing, social context (including the C of others), and other aspects of the individual's personality. We consider methodological implications of the LCP Model.