Chronic diseases carry important psychological and social consequences that demand significant psychological adjustment. The literature is providing increasingly nuanced conceptualizations of adjustment, demonstrating that the experience of chronic disease necessitates adaptation in multiple life domains. Heterogeneity in adjustment is apparent between individuals and across the course of the disease trajectory. Focusing on cancer, cardiovascular disease, and rheumatic diseases, we review longitudinal investigations of distal (socioeconomic variables, culture/ethnicity, and gender-related processes) and proximal (interpersonal relationships, personality attributes, cognitive appraisals, and coping processes) risk and protective factors for adjustment across time. We observe that the past decade has seen a surge in research that is longitudinal in design, involves adequately characterized samples of sufficient size, and includes statistical control for initial values on dependent variables. A progressively convincing characterization of risk and protective factors for favorable adjustment to chronic illness has emerged. We identify critical issues for future research.