Of the three lice (head, body, and pubic louse) that infest humans, the body louse is the species involved in epidemics of louse-borne typhus, trench fever, and relapsing fever, but all the three cause pediculosis. Their infestations occur today in many countries despite great efforts to maintain high standards of public health. In this review, literature searches were performed through PubMed, Medline, Google Scholar, and EBSCOhost, with key search words of "Pediculus humanus", "lice infestation", "pediculosis", and "treatment"; and controlled clinical trials were viewed with great interest. Removing lice by hand or with a lice comb, heating infested clothing, and shaving the scalp were some of the oldest methods of controlling human lice. Despite the introduction of other resources including cresol, naphthalene, sulfur, mercury, vinegar, petroleum, and insecticides, the numbers of lice infestation cases and resistance have increased. To date, viable alternative treatments to replace insecticides have been developed experimentally in vitro. Today, the development of new treatment strategies such as symbiotic treatment and synergistic treatment (antibiotics + ivermectin) in vitro has proved effective and is promising. Here, we present an overview on managing and treating human lice and highlight new strategies to more effectively fight pediculosis and prevent resistance.