The prime roles of mutations in the genes, encoding chloride ion channels, in various human diseases of muscle, kidney, bone and brain, such as congenital myotonia, myotonic dystrophy, cystic fibrosis, osteopetrosis, epilepsy, glioma, etc., have been well established. Chloride ion channels are also responsible for glioma progression in brain and malaria parasite in red blood cells. The present article thus emphasises on the various diseases associated with chloride channel regulation and their modulators. Studies on various chloride channels and their modulators have been discussed in detail.