There is considerable interest in understanding the genetics of erectile dysfunction (ED) and Peyronie's disease (PD) in an effort to identify novel therapeutic and preventative targets. Initial support for a genetic component of ED and PD was derived from familial aggregation studies. Candidate gene studies have suggested an association between polymorphisms of eNOS and ED and between TGF-β1 and PD. More recently, several genome-wide association studies have suggested an association between single-nucleotide polymorphisms of the SIM1 gene and ED. The development of models and functional assays that are able to explore these potential pathways implicated in ED and PD is pivotal for future studies. We highlight the current literature that supports a genetic component for ED and PD. PATIENT SUMMARY: There is great interest in understanding the genetic underpinnings of erectile dysfunction and Peyronie's disease. Candidate gene studies and genome-wide association studies have set a foundation for future work; however, we have yet to determine a true genetic cause. A better understanding of the genetics of these conditions will help advance novel therapeutics and preventative strategies.