Depression is a significant health issue for older Americans. Individuals who exhibit relative left-frontal hypoactivation of the cerebral cortex are at increased risk for developing depression while individuals who are physically active report lower depression scores than their inactive counterparts. Additionally, physical activity has been shown to reduce depression as effectively as pharmacological agents. Purpose: Therefore, this investigation examined both frontal hemispheric brain asymmetry and physical activity as predictors of depression in 76 elderly individuals. Methods: Participants were required to complete the Yale Physical Activity Survey for Older Adults (Dipietro, Casperson, Ostfeld, & Nadel, 1993), The Beck Depression Inventory (BDI, Beck, Steer & Brown, 1996) and electroencephalographic (EEG) recording under both eyes-open and eyes-closed conditions to asses hemispheric asymmetry. It was predicted that individuals with lower asymmetry scores would report higher scores on the BDI while higher levels of physical activity were expected to reduce scores on the BDI. Hierarchical regression analyses were performed separately for both eyes-open and eyes-closed conditions. BDI was entered as the dependent variable, asymmetry as the first predictor and Yale score as the second predictor. Results: For eyes-open, results revealed no predictive value for both asymmetry and physical activity (R2 change = .014, F change = 1.034, p = .313). For eyes-closed, results, again, revealed no predictive value for both asymmetry and physical activity (R2 change = .014, F change = 1.068, p = .305). Conclusions: As such, in this population, hemispheric asymmetry and physical activity were unable to predict depression scores. However, the participants in this investigation were functioning at a very high level and were a relatively homogeneous group. As such, it is necessary to increase the range of individuals to include those who are very active as well as those who are inactive.