Following the discovery that administration of intravenous lipid emulsion (ILE) may reverse the cardiac and neurological toxicity of certain local anesthetic agents, ILE's potential role has recently been explored in the setting of toxicity attributed to a variety of different drugs. The potential mechanisms, safety and efficacy of this approach are considered in this review. Data are reviewed from 76 published reports involving ILE administration for severe drug toxicity, including 55 where toxicity was due to nonanesthetic agents. ILE was reported to exert a positive therapeutic effect in only a proportion of the reported cases, with greatest evidence of efficacy concerning local anesthetic agents. Administration has typically involved bolus administration followed by continuous maintenance infusion, and a number of different mechanisms are proposed, from preferential partitioning of the drug from cardiac tissue to the circulating lipid fraction and direct inotropic effects related to carnitine pathways and fatty acid oxidative metabolism. No major adverse effects have been encountered, but too few data exist to adequately address the safety profile of ILE.