Inflammatory processes are likely to play a causal role in geriatric depression. Geriatric depression occurs in the context of illnesses in which inflammatory processes are part of the pathogenesis. Both aging and depression are associated with immune responses, and the connectivity among mood-regulating structures may be modulated by inflammatory responses. Geriatric depression exacerbates the symptoms of comorbid disorders. Geriatric depression often occurs in persons exposed to chronic stress, a state precipitating geriatric depression and triggering proinflammatory responses. The successful treatment of comorbid conditions that increase central nervous system inflammatory responses has general health benefits and should be part of clinical practice.