In critically ill patients, the duration of effect and dose-response relationship of sedative and analgesic drugs can be significantly affected by the presence of renal or hepatic dysfunction. Alterations in pharmacokinetics and pharmacodynamics vary according to the degree of organ impairment and presence of comorbid illnesses. This article reviews the principals that govern the absorption, distribution, metabolism, and elimination of sedatives and analgesics during renal and hepatic impairment. By anticipating changes in pharmacokinetics, and by routinely assessing the clinical response to therapy, unintended adverse consequences of sedative and analgesic drug therapy may be avoided.