Lifestyle medicine is a burgeoning field of clinical practice that focuses on the prevention of chronic disease development and progression using nonpharmacological and non-procedural interventions. Unfortunately, contemporary medicine is characterized by delaying interventions until symptoms and complications appear in the later chronic disease stages. Moreover, these interventions are mainly pharmacologic and procedural with little attention paid to structured lifestyle change. An awareness and willingness to de-escalate pharmacotherapy are among the most important attitudes to promote lifestyle change. There are many studies that can be reviewed for specific tactics to de-escalate medication while concurrently escalating lifestyle changes such as healthy dietary patterns and physical activity. It is interesting that as populations are found to be sicker (e.g., with higher prevalence rates of multiple chronic diseases) the balance of action favors pharmacotherapy escalation. Imagine scenarios with improved population health where this balance reverses and favors pharmacotherapy de-escalation with greater emphasis on primary lifestyle medicine. Indeed, more clinical trials, educational curricula, and infrastructure are needed to support appropriate pharmacotherapy de-escalation.