Schistosomiasis is not known to be associated with any malignant disease other than bladder cancer. Bladder cancer is still the most common malignant tumor among males in Egypt and some African and Middle East countries. However, the frequency rate of bladder cancer has declined significantly during the last 25 years. This drop is mainly related to the control of Schistosomiasis. Many studies have elucidated the pathogenic events of Schistosomal-related bladder cancer with a suggested theory of pathogenesis. Furthermore, the disease presents with a distinct clinicopathologic profile that is quite different from bladder cancer elsewhere with younger age at presentation, more male predominance, more invasive stages, and occurrence of squamous cell carcinoma pathologic subtype. However, recent data suggest that this profile has been dramatically changed over the past 25 years leading to minimization of the differences between its features in Egypt and that in Western countries. Management of muscle-invasive localized disease is mainly surgery with 5-year survival rates of 30–50%. Although still a debatable issue, adjuvant and neoadjuvant chemotherapy and radiotherapy have improved treatment outcomes including survival and bladder preservation rates in most studies.