The arachidonic acid-prostaglandin pathway has been implicated in many types of malignancies. NSAIDs can inhibit prostaglandin production but concerns about the potential complications of their long-term use have dampened enthusiasm for their use in the prevention and treatment of cancer. Given the vast amount of data implicating the arachidonic acid-prostaglandin pathway in urologic malignancies, a better understanding of the mechanistic contribution of these pathway components to malignancy is necessary to help us determine future priorities and new therapeutic directions. In this review we will summarize the current data on the role of the arachidonic acid-prostaglandin pathway in urologic malignancies and explore some of the mechanistic problems with the use of NSAIDs and the potential for inhibiting other points in the pathway.