A long-held assumption and expectation has been that genomics-based precision medicine will provide clinicians with the tools and therapies they need to consistently deliver the right treatment to the right patient while simultaneously reducing waste and yielding cost savings for health systems. The pace of discovery within the field of precision medicine has been remarkable, yet optimal uptake of new genetic tests and genetically targeted therapies will occur only if payers recognize their value and opt to cover them. Coverage decisions require clear evidence of clinical effectiveness and utility and an understanding of how adoption will impact healthcare costs and utilization within a payer's network. Research in precision medicine has often not considered the payer's perspective, and despite demonstrations of clinical effectiveness for many promising precision medicine innovations, coverage determinations have been deferred because relevant findings that payers can use to make informed decisions are lacking. Collaboration among payers, scientists, and clinicians is essential for accelerating uptake and value creation. By pairing clinical outcomes with claims and cost data and collaboratively conducting well-designed pragmatic clinical or observational studies, all stakeholders can learn from more meaningful and relevant outcomes. In turn, there will be a collective understanding of how precision medicine innovations impact the health of populations and care delivery within healthcare systems.