Arsenic toxicity in humans manifests several outcomes in humans, which include arsenic-induced genomic instability, DNA damage, impaired DNA repair, carcinogenesis, dermatological lesions and other health related problems. Of the 137 million individuals affected, nearly 26 million individuals are in the state of West Bengal, India. Studies have identified dermatological lesions like keratosis, basal cell carcinoma, Bowen’s diseases, squamous cell carcinoma, etc., as key indicators of aggressive arsenic toxicity in humans. Although a large number of individuals are exposed to arsenic but only about 15 to 20 % individuals showed arsenic induced skin lesions. This clearly indicates that genetic susceptibility plays an important role in arsenic susceptibility. Analyses of genetic susceptibility have been carried out to study the prevalence of single nucleotide polymorphisms (SNPs) in number of genes as they might be involved arsenic metabolism and detoxification. It has been observed that a number SNPs in these genes were significantly associated with arsenic induced skin lesions and other health effects. In the present review we try to coalesce the different observations and associations of SNPs with arsenic-induced toxicity, with special emphasis on the study population from West Bengal. We have adopted certain candidate gene approaches to evaluate the association of arsenic-induced toxic outcomes like skin lesions, conjunctival irritations, DNA damage, epimutagenesis, cancer, etc. This review shall be helpful in understanding the importance of genetic make-up of an individual towards evaluating the xenotoxic outcomes, like those in case of arsenic exposure.