The circadian rhythm is an internal timing system, which is generated by circadian clock genes. Because the circadian rhythm regulates numerous cellular, behavioral, and physiological processes, organisms have evolved with intrinsic biological rhythms to adapt the daily environmental changes. A variety of pathological events occur at specific times, while disturbed rhythms can lead to metabolic syndrome, vascular dysfunction, inflammatory disorders, and cancer. Therefore, the circadian clock is considered closely related to various diseases. Recently, accumulated data have shown that the penis is regulated by the circadian clock, while erectile function is impaired by an altered sleep-wake cycle. The circadian rhythm appears to be a novel therapeutic target for preventing and managing erectile dysfunction (ED), although research is still progressing. In this review, we briefly summarize the superficial interactions between the circadian clock and erectile function, while focusing on how disturbed rhythms contribute to risk factors of ED. These risk factors include NO/cGMP pathway, atherosclerosis, diabetes mellitus, lipid abnormalities, testosterone deficiency, as well as dysfunction of endothelial and smooth muscle cells. On the basis of recent findings, we discuss the potential role of the circadian clock for future therapeutic strategies on ED, although further relevant research needs to be performed.Copyright: © 2022 Li et al.