Acute overdose with prescription medications and acute withdrawal syndromes are commonly encountered in the critical care setting. Life-threatening overdoses are usually the result of a suicide attempt, and tricyclic antidepressants are commonly used. Recent literature has focused on objective criteria to determine the prognosis for adverse outcomes.Electrocardiographic findings hold promise for determining patients at highest risk, but further studies are needed to determine which patients may be safely monitored outside of an intensive care unit setting without complications. Other studies have focused on the fatality rates of antidepressants and benzodiazepines when taken in overdose, and this may reflect a trend to change prescribing habits to use less-toxic medications in patients at high risk for suicide. The use of less-toxic medication may lead to fewer fatal overdoses and lessen the burden on critical care resources. A recent review of the toxicity of lithium is discussed. When supportive treatment for overdose fails, hemodialysis is often used, but a new technique known as continuous arteriovenous hemoperfusion may be an alternative therapy. Treatment of acute withdrawal syndromes in the intensive care unit is not standardized and there are no recent studies of protocols. Short-acting cross-tolerant medications should be titrated to relieve withdrawal signs.Many abused drugs do not produce physical dependence and can be treated symptomatically. Once patients have been treated for the acute overdose or withdrawal syndrome, they should be referred for long-term treatment of their underlying disease.