This article addresses conventional pharmacologic and nonpharmacologic treatment of pain in patients in ICUs. For the critically ill patient, opioids have been the mainstay of pain control. The optimal choice of opioid and dosing regimen for a specific patient varies depending on factors such as the pharmacokinetics and physicochemical characteristics of an opioid and the body's handling of the opioid, concomitant sedative regimen, potential or actual adverse drug events, and development of tolerance. The clinician must appreciate that favorable pharmacokinetic properties such as a short-elimination half-life do not necessarily translate into clinical advantages in the ICU setting. A variety of medications have been proposed as alternatives or adjuncts to the opioids for pain control that have unique considerations when contemplated for use in the critically ill patient. Most have been relatively unstudied in the ICU setting, and many have limitations with respect to availability of the GI route of administration in patients with questionable GI absorptive function. Nonpharmacologic, complementary therapies are low cost, easy to provide, and safe, and many clinicians can implement them with little difficulty or resources. However, the evidence base for their effectiveness is limited. At present, insufficient research evidence is available to support a broad implementation of nonpharmacologic therapies in ICUs.