Arsenic is a known toxin and carcinogen that is present in industrial settings and in the environment. The mechanisms of disease initiation and progression are not fully understood. In the last a few years, there has been increasing evidence of the correlation between the generation of reactive oxygen species (ROS), DNA damage, tumor promotion, and arsenic exposure. This article summarizes the current literature on the arsenic mediated generation of ROS and reactive nitrogen species (RNS) in various biological systems. This article also discusses the role of ROS and RNS in arsenic-induced DNA damage and activation of oxidative sensitive gene expression.