Helminths or worms are multicellular organisms living as endoparasites within the human body. Most of these organisms treat human body as definitive host so that parasitic adult-worm stage resides in the intestine. The manifestation of infection varies depending on organ involvement, from skin, intestines to the brain, worm burden, and the species involved. Many infections could be chronic with severe disabilities. The clinically relevant organisms are broadly divided as trematodes (flatworms), cestodes (tapeworms), and nematodes (roundworms). They occur worldwide, though common in tropical countries. The parasitic helminthiasis form significant number among neglected tropical diseases (NTDs). The chemotherapy against helminths is distinct in the sense that these drugs target multicellular organisms unlike bacteria or protozoa. The important group of drugs includes benzimidazoles, macrocyclic lactones, imidazothiazoles, and piperazine derivatives. Albendazole is the mainstay drug for most of the nematodes, except, filariasis, Strongyloides, and Onchocerca infection. Praziquantel is the mainstay drug for most of the trematodes and cestodes, except, Fasciola and Echinococcus. Diethylcarbamazine is used in filariasis. Ivermectin has a significant impact on disease burden of Onchocerca and Strongyloides. Triclabendazole is used in Fasciola and albendazole in Echinococcus.