This study was conducted to provide a narrative overview of interactions between smoking and drug effectiveness/ pharmacokinetics. Database searches were performed to identify review articles published prior to March 10, 2013. Eligible articles reporting altered pharmacokinetic profiles, drug response, or adverse drug effects due to drug-smoking interactions were selected. Information on mechanism of action and clinical effects from the selected articles (n = 83) were summarized by therapeutic drug class. For cardiovascular drugs, smoking effects were variable. Smoking reduced aspirin response but increased clopidogrel response by increasing active metabolites. Warfarin, which has a narrow therapeutic range, required dosage adjustment in smokers due to its rapid clearance. Smoking is a risk factor for respiratory disease, leading to a lower response to corticosteroid and requiring increased doses or additional drugs. Higher doses of theophylline and some antipsychotics, which are mainly metabolized by CYP1A2, are required to reach an optimal plasma concentration in smokers. Smoking is also a risk factor for cancer, especially for lung cancer. Erlotinib or gefitinib are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer and showed lower anticancer effects in smokers. This summary of the interactions between smoking and drug pharmacological properties will aid healthcare professionals in providing patients with appropriate drug therapies, and emphasizes the need for considering smoking status as a patient factor in the clinical setting.