Homelessness is a major social and public health problem worldwide. The prevalence of body lice in sheltered homeless persons varies from 7% to 22%, and decreasing the burden of body lice infestation among homeless persons may prevent infectious disease outbreaks. Classic therapeutic measures for body lice infestation have shown little success. In this randomized, double-blind, placebo-controlled trial, Benkouiten et al demonstrate that permethrin-impregnated underwear reduced body lice infestations at day 14, but this was not sustained by day 45. The use of permethrin may have increased permethrin resistance in body lice, and the authors suggest that this strategy should be avoided.