Several commonly used medications impair mitochondrial function resulting in adverse effects or toxicities. Drug induced mitochondrial dysfunction may be a consequence of increased production of reactive oxygen species, altered mitochondrial permeability transition, impaired mitochondrial respiration, mitochondrial DNA damage or inhibition of beta-oxidation of fatty acids. The clinical manifestation depends on the specific drug and its effect on mitochondria. Given the ubiquitous presence of mitochondria and its central role in cellular metabolism, drug-mitochondrial interactions may manifest clinically as hepatotoxicity, enteropathy, myelosuppression, lipodystrophy syndrome or neuropsychiatric adverse effects, to name a few. The current review focuses on specific drug groups which adversely affect mitochondria, the mechanisms involved and the clinical consequences based on the data available from experimental and clinical studies. Knowledge of these adverse drug-mitochondrial interactions may help the clinicians foresee potential issues in individual patients, prevent adverse drug reactions or alter drug regimens to enhance patient safety. Copyright ? 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.