Anthropogenic sources of arsenic poses and creates unintentional toxico-pathological concerns to humans in many parts of the world. The understanding of toxicity of this metalloid, which shares properties of both metal and non-metal is principally structured on speciation types and holy grail of toxicity prevention. Visible symptoms of arsenic toxicity include nausea, vomiting, diarrhea and abdominal pain. In this review, we focused on the dermal cell stress caused by trivalent arsenic trioxide and pentavalent arsanilic acid. Deciphering the molecular events involved during arsenic toxicity and signaling cascade interaction is key in arsenicosis prevention. FoxO1 and FoxO2 transcription factors, members of the Forkhead/Fox family, play important roles in this aspect. Like Foxo family proteins, ATM/CHK signaling junction also plays important role in DNA nuclear factor guided cellular development. This review will summarize and discuss current knowledge about the interplay of these pathways in arsenic induced dermal pathogenesis.