The need for compassionate care of the critically ill often compels clinicians to treat these patients with pharmacologic sedation. Although patients may appear to be asleep under the influence of these sedating medications, the relationship between sleep and sedation is complex and not fully understood. These medications exert their effects at different points along the central nervous system's natural sleep pathway, leading to similarities and differences between the two states. This relationship is important because critically ill patients sleep poorly and this phenomenon has been linked to poor intensive care unit outcomes. Therefore, greater awareness of the effects of these medications on sleep may lead to sedation protocols that further improve outcomes. This article reviews the relationship between sedation and sleep from physiologic and clinical perspectives.