The practice of clinical neuropsychology has traditionally accorded limited attention to the impact of prescription medications on cognitive functioning. Though neuropsychologists see a wide array of patients with cerebropathologic and other organ system disease that are under pharmacotherapy, systematic attention to how these compounds potentially affect neuropsychological functioning has lagged. Psychomotor functioning, concentration, and memory are the most common cognitive domains negatively affected by such medications. In general sedative, psychomotor, and, to a lesser extent, attention/concentration effects covary and typically show tolerance with sustained drug administration. Memory effects are more resistant probably due to ongoing anticholinergic effects and the established link between the cholinergic system and memory functioning. This review covers the basic science and clinical literature addressing neuropsychological functioning both in healthy nonpatients and in patients treated with antidepressants, anxiolytics, stimulants, antihypertensives, antiepileptics and antihistamines. Critical to the understanding of the effects of these agents is the integration of multiple factors that modulate medication-induced neurocognitive effects, such as chronicity of treatment, tolerance, age, ethnicity, metabolic capacity, psychological, and neurological disorders in the patient, and the benefits of successful treatment of these disorders.