Low cardiorespiratory fitness (CRF) is a well-established risk factor for all-cause and cardiovascular disease mortality. African Americans have higher rates of cardiovascular disease compared with their Caucasian counterparts. However, the extent to which lower CRF levels contribute to the excess risk in African Americans has not been fully explored. The purpose of this review is to: (i) explore the literature evaluating the relationship between CRF and mortality specifically in African American populations; and (ii) critically evaluate the studies which have compared CRF between African American and Caucasians in epidemiological studies and clinical trials. We have further discussed several potential mechanisms that may contribute to the observation of lower CRF levels in African American compared with Caucasian adults, including potential racial differences in physical activity levels, muscle fiber type distribution, and hemoglobin levels. If lower CRF is generally present in African Americans compared with Caucasians, and is of a clinically meaningful difference, this may represent an important public health concern.