Cr(VI)-containing compounds are known carcinogens that are present in industrial settings and in the environment. The biological mechanisms responsible for the initiation and pregression of diseases resulting from exposure to Cr(VI) are not fully understood. In the last two decades, there has been increasing evidence of the correlation between Cr(VI)-induced generation of reactive oxygen species and carcinogenic actions. This article summarizes the current literature on Cr(VI)-induced generation in various chemical and biological systems. This article also covers the relationship between Cr(VI)-induced oxidative stress and activation of transcription factors NF-kappaB, AP-1, p53, and hypoxia-inducible factor 1, regulation of cell cycle, and induction of apoptosis.