The incidence of toxic effects of drugs leading to emergency department visits has increased in the United States in the past several years. Most of these patients can be adequately managed by supportive care alone. However, pharmacological antidotes may be necessary, particularly in patients with hemodynamic instability. In severe cases refractory to conventional antidote therapy, rescue therapy with intravenous lipid emulsion (ILE) may be necessary. Traditionally, ILE has been used as an antidote of choice in treating toxic effects of local anesthetics. But data continue to emerge on the successful use of ILE to treat overdoses of drugs other than local anesthetics, particularly lipophilic medications. The recommended ILE dose is a 1.5 mL/kg bolus followed by infusion of 15 mL/kg per hour, with repeat dosing permissible for continued hemodynamic instability. Use of ILE should be considered early as a rescue therapy in the settings of lipophilic medication overdoses when cardiovascular compromise or cardiac arrest is present.