Phosphodiesterase type 5 (PDE5) inhibitor is the drug of choice for the treatment of erectile dysfunction. It selectively inhibits the activity of PDE5, reduces the degradation of cGMP, and causes the vasodilation of the corpus cavernosum, thereby maintaining the male erectile response. At present, some studies have shown that the mechanism of action of PDE5 inhibitor may affect the signaling pathways of skin cells, leading to an increased risk of melanoma in patients. In addition, many epidemiological studies have also evaluated the association between PDE5 inhibitor and the risk of melanoma, but no clear consensus has yet been reached. This article reviews the progress of the above research.