African Americans are more likely to be diagnosed with and die as a result of colorectal cancer than white patients. This review briefly documents these differences and explores the factors that may contribute to advanced stage at diagnosis and reduced survival once African Americans are diagnosed with colorectal cancer. Attention is focused on what is known about the role of socioeconomic status, cancer screening, comorbidities and lifestyle factors, tumor biology and genetics, and the differences in the receipt of and benefit of appropriate therapy. Finally, areas of ongoing and future research and policy initiatives aimed at reducing disparities are discussed.