IMPORTANCE Long-term longitudinal studies are needed to delineate the trajectory of depressive symptoms across adulthood and to individuate factors that may contribute to increases in depressive symptoms in older adulthood. OBJECTIVES To estimate the trajectory of depressive symptoms across the adult life span; to test whether this trajectory varies by demographic factors (sex, ethnicity, and educational level) and antidepressant medication use; and to test whether disease burden, functional limitations, and proximity to death explain the increase in depressive symptoms in old age. DESIGN Longitudinal study. SETTING Community. PARTICIPANTS The study included 2320 participants (47.0%female; mean [SD] age at baseline, 58.1 [17.0] years; range, 19-95 years) from the Baltimore Longitudinal Study of Aging. MAIN OUTCOMES AND MEASURES Estimated trajectory of depressive symptoms modeled from 10 982 assessments (mean [SD] assessments per participant, 4.7 [3.6]; range, 1-21) based on the Center for Epidemiologic Studies Depression scale and 3 subscales (depressed affect, somatic complaints, and interpersonal problems). RESULTS The linear (?10 = 0.52; P > .01) and quadratic (?20 = 0.43; P > .01) terms were significant, which indicated that depressive symptoms were highest in young adulthood, decreased across middle adulthood, and increased again in older adulthood. The subscales followed a similar pattern.Women reported more depressed affect at younger ages, but an interaction with age suggested that this gap disappeared in old age. Accounting for comorbidity, functional limitations, and impending death slightly reduced but did not eliminate the uptick in depressive symptoms in old age. CONCLUSIONS AND RELEVANCE Symptoms of depression follow a U-shaped pattern across adulthood. Older adults experience an increase in distress that is not due solely to declines in physical health or approaching death.