Evidence-based guidelines are important sources of knowledge in everyday clinical practice. In 2005, the German Society for Urology decided to develop a highquality evidence-based guideline for the early detection, diagnosis and treatment of the different clinical manifestations of prostate cancer. The guideline project started in 2005 and involved 75 experts from 10 different medical societies or medical organizations including a patient organization. The guideline was issued in September 2009 and consists of 8 chapters, 170 recommendations, and 42 statements. Due to the broad spectrum of clinical questions covered by the guideline and the high number of participating organizations and authors, the organizers faced several methodological and organizational challenges. This article describes the methods used in the development of the guideline and highlights critical points and challenges in the development process. Strategies to overcome these problems are suggested which might be beneficial in the development of new evidence-based guidelines in the future.