Arsenic is a potent human carcinogen, which affects millions of people around the world causing deleterious health impacts including cancer and death. In India, West Bengal is the worst affected state where more than 26 million people are exposed chronically to arsenic by drinking heavily contaminated ground water. Several hypotheses have been associated with arsenic-induced carcinogenesis including chromosomal abnormalities, oxidative stress, altered DNA repair, p53 gene suppression, gene amplification, transformation and altered growth factors leading to increased cell proliferation and carcinogenesis. In addition to that, it has been hypothesised that altered DNA methylation patterns might contribute to arsenic-induced carcinogenesis. Even then, the mechanisms leading to arsenic-induced carcinogenesis are poorly understood. We have been trying to identify the contenders that contribute to arsenic susceptibility, toxicity and carcinogenicity in the arsenic exposed rural population of West Bengal. In this article, attempts have been made to summarise the work that we have carried out so far in the said human population exposed to arsenic through drinking water.