Head lice infestation is a common and growing problem, primarily affecting school-aged children. There are growing numbers of treatment failures due to the emergence of treatment-resistant lice to the popular over-the-counter products that have been used for the past several decades. Resistance has also decreased the efficacy of lindane, a prescription pediculicide that has been commonly used for several generations. Malathion, recently reintroduced in the US as a prescription pediculicide, has been associated with some treatment resistance depending upon its formulation. Other insecticidal treatments, such as ivermectin, will have to be developed further, given the limited options presently available for the treatment of head lice. Given the number of anecdotal and market-driven reported studies on head lice, assessment of topical lice therapies requires standardised in vitro testing. Based on concerns about safety and decreasing efficacy due to resistance, a reassessment of the general topic of pediculicides for head lice is warranted.