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Introduction: Erectile dysfunction is among the most prevalent urologic issues affecting men globally and is characterized by a high incidence rate. This condition significantly affects the quality of life of patients and their sexual partners., Objectives: Due to the interactions, contraindications, and side effects associated with systemic drugs, recent research has increasingly focused on topical and transdermal medications for the treatment of erectile dysfunction., Methods: Based on previous studies, this article examines papaverine in terms of local effectiveness, methods of increasing therapeutic efficiency, possible local side effects, and evaluation of its various formulations., Results: Among these approaches, notable strategies include using novel formulations and nanoformulations as compared with classic ones, employing permeation enhancers, and combining treatments with other oral and topical drugs with synergistic mechanisms. These methods aim to improve transdermal papaverine's bioavailability and therapeutic efficacy while minimizing side effects and enhancing patient compliance., Conclusion: Transdermal papaverine may not be as effective as its injectable form, but the treatment path is more pleasant, with less pain and fewer side effects for patients. For this reason, using solutions that remove the penile skin and fascial absorption barrier can be very effective., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)