Many agents are available for sedation of agitated, delirious patients. In general, they should be administered intravenously to achieve a painless, more rapid, and more reliable onset of action. Proper selection of an agent requires understanding the basic principles discussed in this article, including the T-1/2 alpha and T-1/2 beta and the side-effect profile associated with each class of drugs, as well as for each agent. As a group, BNZs tend to be the safest and most predictable, and can be titrated easily when administered intravenously. Neuroleptic agents such as haloperidol may act synergistically with BNZs, resulting in control of agitation without significantly depressing the patient's level of consciousness or respiratory drive. Barbiturates, highly effective sedatives, more profoundly depress the respiratory and cardiovascular systems, and probably should be reserved for the severely agitated patient who cannot be controlled otherwise. Etomidate and propofol, useful for short-term procedures, probably should be avoided for long-term use in the agitated patient because of potentially serious side effects. Opioids should be used to provide adequate pain relief and to supplement other sedatives. Inadequate doses or dosing regimens should be avoided. Once sedation has been achieved, control usually can be maintained with continuous intravenous infusions of BNZs, perhaps in combination with a continuous infusion of an opioid or intermittent administration of a neuroleptic agent. With goal-oriented titration of the pharmacologic therapy, patients can be maintained safely in a sedate, calm state; intermittent periods of agitation, alternating with periods of severely depressed level of consciousness, can be avoided. Finally, when pharmacologic suppression of agitation and delirium is needed, the patient must be evaluated fully to determine the underlying cause of the confusional state.