Fatalism has been identified as a crucial barrier to participation in cancer screening among African Americans. The essence of fatalism is woven throughout the lived experience for some African Americans. Therefore, to fully understand its impact, fatalism must be viewed within its broadest historical and sociocultural context. This article explores the philosophical origins and the practical significance of fatalism with regard to cancer screening among this population. Health care professionals must position themselves to promptly identify fatalistic persons. Interventions to successfully negate the influence of fatalism are needed.