Head lice infestation is a common and growing problem that primarily affects school-aged children. Most cases of head lice are diagnosed and treated by nonphysicians. Misdiagnosis may lead to treatment when no lice are present. Treatment failure may lead to repeated use of and improperly applied pediculicides, potentially resulting in overexposure to pesticides. These treatment failures are primarily due to the emergence of treatment-resistant lice. In regions where resistant lice are common, patients may self-treat numerous times with over-the-counter pediculicides before seeking treatment from a physician. Resistance has decreased the efficacy of lindane, a prescription pediculicide that has been used for decades. In addition, the Food and Drug Administration recently warned of potentially serious adverse effects associated with lindane and recommended strict controls for its use. Malathion, recently reintroduced in the United States as a prescription pediculicide, has not been associated with treatment resistance or notable adverse effects, although it is flammable due to its alcohol base. Because of concerns about decreasing efficacy due to resistance and safety concerns about over-the-counter products and some prescription pediculicides, a reassessment of pediculicide safety is warranted. The safety and efficacy of commonly used over-the-counter and prescription pediculicide products are discussed, along with the safety and efficacy of other treatments, such as ivermectin, that are not indicated for the treatment of head lice but are being used increasingly.