Depression, a heterogeneous disease often accompanied by significant medical and psychiatric comorbidity, is common among the elderly. Clinicians caring for depressed elders should look for comorbidities, as they may affect management of the patient. For example, comorbid anxiety may represent a more difficult to treat syndrome, while inadequately treated depression with comorbid cardiovascular disease has a greater risk of cardiovascular-associated mortality. Comorbidities such as Alzheimer’s dementia and cerebrovascular disease may provide insight into the pathogenesis of late-life depression. This review highlights these comorbid conditions as they occur in depressed elders. Recommended directions for future research in the area of late-life depression are provided.