The importance of mitochondrial dysfunctions in the progression of chronic disease has been well established. Patients with chronic diseases are often prescribed a variety of medications, many of which have been shown to induce mitochondrial dysfunction. Exercise is a known stimulus for mitochondrial biogenesis and also recommended to patients as a lifestyle modification to supplement drug therapy. However, the potential interference of those drugs with mitochondrial adaptations to exercise has not been thoroughly investigated. This review provides a summary and discussion of known and potential interactions of commonly consumed drugs with exercise-induced mitochondrial adaptations.