Colorectal cancer (CRC) is the third most common cause of cancer deaths among men in the United States. Although CRC screening has been found to reduce CRC incidence and mortality, current screening rates among men are suboptimal due to various practical and psychosocial barriers. One potential barrier to CRC screening identified in qualitative studies with men is the threat to masculinity that endoscopic screening methods pose. Indeed, beliefs about masculinity have been predictive of other preventive health behaviors among men. In this review article, we propose a novel conceptual framework to explain men’s CRC screening behavior that integrates masculinity norms, gender role conflict, men’s health care experiences, behaviors, and beliefs, and social and background variables. This framework has the potential to guide future research on men’s CRC screening behaviors and other health behaviors and may inform gender-sensitive interventions that target masculinity beliefs to increase preventive health behaviors.