Necator americanus is a nematode hookworm of the family Ancylostomatidae, subfamily Necatorinae. This nematode parasite, which is distinguished by two chitinous cutting plates in the buccal cavity and fused male copulatory spicules, is the causative agent of necatoriasis, a hookworm disease prevalent in the Americas as well as in the tropical regions of Africa, southern Asia, and Polynesia. The adult parasites attached to the villi of the small intestines will suck blood causing abdominal discomfort, diarrhea and cramps, anorexia, wight loss, and in advanced disease, hypochromic microcytic anemia. Hookworm infections in man, especially in children, are one of the leading causes of iron-deficiency anemia resulting directly from intestinal capillary blood loss following the feeding activities of fourth-stage (L4) larva and adult worms. Another clinical manifestation often associated with hookworm infections is cutaneous larva migrans (CLM). It is a well recognized, usually self-limiting condition caused by the infectious larvae of nematodes. CLM is characterized by skin eruption and represents a clinical description rather than a definitive diagnosis. Of the hookworm parasites, the dog and cat worm Ancylostoma braziliense is the most common causing CLM, although many other species have been implicated. The major subject of this review article will be discussion of the evolution of therapies and treatment of human necatoriasis and the development of experimental infections with N. americanus. Difference in the clinical efficacies of mebendazole and albendazole will be discussed along with drug resistance of N. americanus.