Arsenical-induced carcinogenesis in human bladder has been established through epidemiological evidence, and UROtsa cells, a normal, immortalized cell culture model of human urothelium, have proven to be a good model for the bladder epithelium. This cell line does not form tumors when injected into immuno-compromised mice nor does it have anchorage-independent growth. UROtsa can be easily manipulated for acute studies related to arsenical exposure. They have been shown to be sensitive to all arsenicals, in particular, the trivalent species, arsenite and monomethylarsonous acid. UROtsa cells have also opened the area of cellular signaling alterations following subcytotoxic exposure to arsenicals in both the acute and long-term time points. In addition, UROtsa cells were shown to be malignantly transformed following low-level exposure to both As(III) and MMA(III) providing additional models for studying arsenical-induced carcinogenesis of the bladder. These transformed cell lines allow researchers the ability to investigate the process of urothelial tumorigenesis at multiple time points of arsenical exposure. Overall, UROtsa cells are an effective model for cellular insult following arsenical exposure.