The relation between Schistosomiasis and bladder cancer is well-established and accounts for the high rates of bladder cancer in a number of developing countries, including Egypt. In developed countries, transitional cell carcinoma is the predominant type of bladder cancer, whereas in Schistosomiasis-endemic regions, squamous cell carcinoma is the most common type. In this review, experimental and observational data on infection, inflammation, and bladder cancer are summarized with special emphasis on transitional cell carcinoma. Findings from numerous studies suggest that inflammation is likely to have an important role in bladder carcinogenesis in developed countries. Future studies need to focus in greater detail on risk factors that increase inflammation of the bladder, examine genetic susceptibility to inflammatory pathways, and include markers of inflammation measured prior to cancer diagnosis. Understanding the role of inflammation on transitional cell carcinogenesis may provide important insights on how to prevent the sixth most common cancer in the United States.