Polypharmacy, the simultaneous use of multiple medications, is growing at an alarming rate with reports documenting a range of 12 to 22 prescriptions being used on average by individuals >50 years of age.  Before we can tackle the problem we must recognize it and its root causes. The healthcare consequences of polypharmacy range from drug-drug interactions, adverse drug events, prescribing cascades, chronic dependence and hospitalizations, all of which have significant health and economic consequences.  Recent attention on precision medicine and personalized therapeutics, along with advanced health informatics technology, provides a focus needed to manage this condition and avoid its multiple complications. We will discuss the continuum of problems associated with polypharmacy, its basis, and the role pharmacogenomics plays in providing solutions. The important role of clinical laboratories as major enablers of precision, personalized medicine will be discussed. Laboratory medicine as a discipline has the potential to deliver a much needed precision approach to pharmaco-therapeutics.