Patient-focused sedation and analgesia in the ICU encompasses a strategy of comprehensive structured management that matches initial evaluation, monitoring, medication selection, and the use of protocols with patient characteristics and needs. This is best accomplished through interdisciplinary management by physicians, nurses, and pharmacists. An early consideration is that of the potential predisposing and precipitating factors, as well as prior sedative or analgesic use, factors that may influence pharmacologic and supportive therapy. Frequent monitoring with validated tools improves communication among clinicians and plays an important role in detecting and treating pain and agitation while avoiding excessive or prolonged sedation. Patient-focused management encompasses selecting medications best suited to patient characteristics, including the presence of organ dysfunction that may influence drug metabolism or excessive risk for side effects. The use of protocols to optimize drug therapy has emerged as a key component of management, resulting in reductions in the duration of sedation, mechanical ventilation, and ICU length of stay demonstrated with strategies to titrate medications to specific targets, daily interruption of sedation, intermittent rather than continuous therapy, and analgesia-based therapy. While much attention is paid to the initiation and maintenance of therapy, greater emphasis must be placed on careful de-escalation of therapy in order to avoid analgesic or sedative withdrawal. Finally, more work is needed to explore the relationship of critical illness and sedation management with long-term psychological outcomes.