The potential for abuse of medications that are controlled substances is well known. Abuse of certain noncontrolled prescription drugs and over-the-counter medications also may occur. To some degree, any medication that exerts psychoactive effects may be abused if taken in high enough doses or by means that result in high serum or cerebrospinal fluid levels. Many clinicians may be unaware of the potential for abuse of these medications. This review examines evidence of the possibility of abuse of several common medications that theoretically do not have abuse potential, including cough and cold preparations, antihistamines, anticholinergics, antipsychotics, antidepressants, anticonvulsants, skeletal muscle relaxants, and antiemetics. Means by which such medications may be abused and biochemical and physiological mechanisms fostering their abuse also are discussed.