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The discovery of biological targets in the fibrosis pathway has led to the advent of many potential therapies for fibrotic diseases. During the last 2 decades an increasing number of large, randomized studies on antifibrotic medications in urology have evaluated its efficacy, safety and long-term outcomes. Although there are many established therapeutics with antifibrotic properties, we focused on the 6 antifibrotic agents that are most currently relevant to the field of urology, including clostridial collagenase histolyticum, mitomycin C, halofuginone, triamcinolone acetonide, verapamil and interferon. We evaluate and summarize the existing published literature on these antifibrotic drugs with a particular emphasis on their safety and efficacy in urological diseases.Using the MEDLINE® database, Cochrane Library Central Search, Web of Science and Google Scholar we reviewed all published articles from 1976 to 2016 using the search terms antifibrotics and urology. The literature was searched for pharmaceuticals with antifibrotic properties and efficacy in urological disease, and the 6 most extensively researched drugs were documented. These antifibrotic drugs were then individually reviewed using the databases previously mentioned, and the safety, efficacy and long-term outcomes of each drug were analyzed and summarized.Our search yielded 63 peer reviewed publications on the use of antifibrotic agents in the field of urology. Clostridial collagenase histolyticum has been studied the most thoroughly in this group, with 19 articles and Food and Drug Administration approval for use in Peyronie's disease. The majority of the publications was prospective or randomized controlled studies. Mitomycin C and triamcinolone acetonide can reduce urethral stricture recurrence at a mean followup period of 1 to 2 years and mitomycin C has been effective in curing recurrent bladder neck contractures. Halofuginone and verapamil have shown efficacy for Peyronie's disease and urethral stricture.This systematic review summarizes the existing literature on the use of antifibrotic drugs for urological disease. Safety, efficacy and long-term outcomes for each drug are evaluated for various disease types and current recommendations for use are reviewed. This systematic review also details the potential therapeutic roles of several antifibrotic medications for treating common urological conditions and diseases, showing that they can be important, useful and effective additions to the urologist's armamentarium.