INTRODUCTION: Erectile dysfunction (ED) is among the most prevalent urologic issues affecting men globally, with a notably high incidence rate. It significantly impacts the quality of life of patients and their sexual partners. OBJECTIVES: Given the increasing prevalence of ED among men in recent years, numerous pharmacotherapies have been developed to address these conditions. However, systemic drug therapies for ED are often associated with significant challenges, including drug interactions and contraindications across a wide range of medical conditions. This has prompted researchers to focus on designing drugs and dosage forms that maintain efficacy while reducing side effects, interactions, and contraindications. METHODS: Building on previous studies, this article investigates nitrates and NO-donors with a focus on their transdermal impact, strategies for enhancing therapeutic efficiency, potential local side effects, and the evaluation of various formulations. RESULTS: In this regard, organic nitrates such as nitroglycerin and isosorbide dinitrate and NO donors comprising volatile alkyl nitrites, linsidomine, sodium nitroprusside, and L-arginine are among good candidates for transdermal formulations of ED treatment. In the current article, the topical effects of these compounds, both alone and in combination with other drugs, have been thoroughly examined, including aspects such as their mechanism of action, effectiveness, side effects, and contraindications. CONCLUSION: Based on these findings, it appears that novel formulations with enhanced absorption of these compounds could play a significant role in the treatment of ED, either as a standalone therapy or as an adjunctive treatment. Currently, most of the data are from preclinical studies and future clinical research can reveal the precise efficacy of such transdermal formulations.