The National Institutes of Health defines precision medicine as “an innovative approach that takes into account individual differences in patient’s genes, environment, and lifestyles. Another form of “personalized medicine” that is “rooted in the belief that since individuals possess nuanced and unique characteristics at the molecular, physiological, environmental exposure and behavioral levels, they may need to have interventions provided to them for diseases they possess that are tailored to these nuanced and unique characteristics.” Race is only a social construct, yet study after study reveals substantial clinical outcome differences that are frequently most significant when stratified by race. Ancestral genomic research is providing clues as to why we see some of the disparities that exist today. This chapter provides a framework to help clinicians understand the far-reaching impact of poor clinical outcomes on African Americans but, more importantly, advance evidence-based solutions that will improve your clinical care. It is no longer just hospitals and healthcare organizations that are penalized for costly and poor outcomes; it now includes clinicians. Applying a precision medicine approach to the care of African Americans will transform your practice.