Certain physiological changes caused by aerobic exercise can alter the pharmacokinetics of some drugs. A systematic review of the pharmacokinetic changes that can affect drugs as a result of aerobic exercise is provided. Eleven commonly used drugs are reviewed for their potential interaction with exercising patients. Serum concentrations of two β-blocking agents, atenolol and propranolol, and one antibiotic, doxycycline, have shown to increase as a result of exercise. No pharmacokinetic changes have been found in exercising patients taking carvedilol or verapamil. Patients who exercise after taking digoxin experience a decreased digoxin serum concentration with an increased skeletal muscle concentration. The clearance of theophylline has been shown to decrease resulting in an increase in plasma half-life during exercise. The risk of hypoglycaemia may increase when patients with diabetes mellitus inject insulin into a muscle just prior to exercising that muscle. Increasing physical activity in patients taking warfarin has been shown to decrease the international normalised ratio. Much is still unknown regarding the interactions that exist between exercise and drug therapy. More studies need to be completed in this area before definite conclusions are made and clinical relevance can be established. Clinicians should be aware that the potential for such interactions exists, especially for drugs with a narrow therapeutic range and in patients who participate in extreme sporting activities.