Pharmacogenomics represents a potentially powerful enhancement to current wellness and medication risk management programs. However, challenges must be addressed to successfully implement these programs especially in large populations where the members and their prescribing physicians are naïve or misinformed to the utilization of genetics for personalized prescribing. We will describe the population assessment, program implementation, and outcomes for a 35,000 member, state-run, Medicare-eligible retiree population, and its relevance across poly-pharmacy and working well populations.