Erectile dysfunction (ED) affects every second man between 40 and 70 years of age. Risk factors for ED such as age, metabolic syndrome, and curative therapies for prostate cancer are increasing, so the prevalence is expected to rise in the coming years. Oral pharmacotherapy with phosphodiesterase type 5-inhibitors (PDE5-Is) is the first-line therapy for ED. However, drug–drug interactions, applications errors, and non-responders (especially higher failure rates in diabetics and post-prostatectomy) lead to inadequate results and discontinuation rates of around 50%, even in the first year of use. Moreover, the treatment options to date are purely symptomatic. Regenerative therapies such as stem cell therapy have the potential to treat ED curatively. Intracavernous stem cell application has already been confirmed to have a high level of safety and tolerance. In human, adipose tissue has the most mesenchymal stem cells per volume. After isolation, the adipose tissue-derived stem cells (ADSCs) can be applied immediately. Intracavernously injected, they can differentiate into cells from neuronal, endothelial, and smooth muscle tissue, i.a., and potentially restore organic dysfunctions. The bioavailability of the erection-promoting neurotransmitter nitric oxide (NO) increases due to the regenerative effect of ADSCs. NO is also the basis for the effect of PDE5-Is. A combined therapy of intracavernous injected stem cells and oral PDE5-Is could therefore be the best possible therapy for erectile dysfunction.