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After decades have past in the field of Pharmacogenetics, overcoming barriers to adoption by providers utilizing pharmacogenetic testing (PGx) is gaining maturity. Readily available resources, including technology advances, reduction in costs, and insurer reimbursements are accelerating PGx testing as a new standard. In this article, they describe preemptive genotyping to optimize medications. In the back of a patients mind when facing a medication change, spoken or not, is "will this prescription change be my best med?" From common maintenance, multiple or high risk medications, standard genotyping results prior to prescribing decisions including genetics should be considered in the plan of a patient's care. This review describes common elements for RX Alerts utilizing genotyping and presents key process applications including clinical decision guidance.