Introduction Despite recent advances in our knowledge and treatment strategies in Peyronie's Disease (PD), much remained unknown about this disease. Aim To provide a clinical framework and key guideline statements to assist clinicians in an evidence-based management of PD. Methods A systematic literature search was conducted to identify published literature relevant to PD. The search included all relevant articles published up to June 2015, including preclinical studies and published guidelines. References used in the text were assessed according to their level of evidence, and guideline recommendations were graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Owing to the paucity of larger series and randomized placebo-controlled trials with regard to surgical intervention, guideline statements are provided as clinical principle or expert opinion. Main Outcome Measures This literature was discussed at a panel meeting, and selected articles with the highest evidence available were used to create consensus guideline statements for the Fourth International Consultation on Sexual Medicine guidelines on PD. Results In addition to existing Third International Consultation on Sexual Medicine guidelines on PD, seven new summary recommendations were created. Conclusion A greater understanding of the scientific basis of PD is greatly needed to address our understanding of the pathophysiology, clinical epidemiology, psychosocial, and diagnostic assessment as well as treatment strategies.