Context: Treatment for depression can be expensive and depression can affect the use of other medical services, yet there is little information on how depression affects the prevalence of cost-related medication nonadherence (CRN) in elderly patients and patients with disabilities. Objective: To quantify the presence of CRN in depressed and nondepressed elderly Medicare beneficiaries and nonelderly Medicare beneficiaries with disabilities prior to the implementation of the Medicare Drug Benefit. Design and Setting: 2004 Medicare Current Beneficiary Survey. Participants: Depressed and nondepressed elderly Medicare beneficiaries and beneficiaries with disabilities. Main Outcome Measures: Cost-related medication nonadherence included taking smaller doses or skipping doses of a prescription to make it last longer, or failing to fill a prescription because of cost, controlling for health insurance status, comorbid conditions, age, race, sex, and functional status. Results: In a nationally representative sample of 13 835 noninstitutionalized elderly Medicare enrollees and Medicare enrollees with disabilities, 44% of beneficiaries with disabilities and 13% of elderly beneficiaries reported being depressed during the previous year. Among enrollees with disabilities reporting depressive symptoms, 38% experienced CRN compared with 22% of enrollees with disabilities who did not report depressive symptoms. Among elderly enrollees who reported depressive symptoms, 19% experienced CRN, compared with 12% of elderly enrollees who did not report such symptoms. In adjusted analyses, depressive symptoms remained a significant predictor of CRN in both groups (persons with disabilities: odds ratio, 1.7; 95% confidence interval, 1.3-2.3; elderly persons: odds ratio, 1.4; 95% confidence interval, 1.1-1.7). Conclusions: Depressive symptoms were associated with CRN in elderly Medicare enrollees and Medicare enrollees with disabilities. Providers should elicit information on economic barriers that might interfere with treatment of Medicare beneficiaries with depression.