Erectile dysfunction (ED) is a common disease in men, and the causes include organic diseases, psychosomatic factors, and endocrine factors. It is not life-threatening, but it has a huge impact on the quality of life of patients and their spouses. With the continuous progress of people’s living standards, more and more people are concerned about the quality of life, so the treatment of ED is gradually gaining the attention of both doctors and patients. The discovery of sildenafil, a PDE5 inhibitor, in 1998 ushered in a “spring” in ED treatment. Large-scale clinical studies have confirmed that ED patients can use up to 70-80% efficiency, and take safe and effective, so soon popular worldwide. Countless male friends from different channels know about “Viagra”, know about this “magic blue pill”, Taiwan Sildenafil trade name “Will Kong”, in everyone The impression is that as long as you eat a pill before sex, you seem to be able to “stay alive”. The company’s main business is to provide a wide range of products and services to the public. But male doctors will tell readers: these are all misconceptions, caused by a lack of understanding of the physiological mechanism of penile erection and the pharmacological action mechanism of sildenafil. The arterial vessels of the male penis secrete a neurotransmitter called nitric oxide after sexual stimulation, which can produce a substance called cyclic guanosine monophosphate by activating proteases, and this substance can produce a diastolic effect on the blood vessels, thus causing our penis to erect. Under physiological conditions, guanosine cyclic phosphate in the penis is quickly metabolized by the enzyme PDE5, thus restoring the penis to a weak state. Sildenafil maintains an erect penis by inhibiting the PDE5 enzyme and reducing the metabolism of guanosine cyclic phosphate. So a PDE5 inhibitor is not a “sex drug”, nor does it enhance sexual performance, and it may be useless for a person who has no sexual desire at all. This is why sildenafil is taken 30 minutes to an hour before the start of sex, in order to increase the effectiveness of the drug by increasing sexual stimulation. Doctors later found that about 30% of ED patients did not respond to PDE5 inhibitors taken on demand, and animal studies and clinical studies revealed that these patients also had vascular endothelial dysfunction, resulting in reduced nitric oxide synthesis. To illustrate, if we compare our penile erection to a bathtub with water, PDE5 inhibitors as the plug at the bottom of the bathtub, and endothelial production of nitric oxide as the water coming out of the faucet, these patients are like a broken faucet with little water coming out, even if we tighten the bathtub plug, it is difficult to fill the bathtub with water. Therefore, for ED patients with vascular endothelial dysfunction, on-demand PDE5 inhibitors are often difficult to achieve therapeutic results. The discovery of the long-acting PDE5 inhibitor tadalafil has since brought about a revolution in treatment modalities for ED patients, namely the small-dose long-term treatment paradigm. Animal and clinical studies have found that tadalafil 5mg or 10mg daily not only has good therapeutic efficacy and safety in ED, but it can maintain the number of penile smooth muscle cells by improving vascular endothelial function, resulting in long-term improvement in erectile function in ED patients even after the end of treatment. In addition, the longer half-life allows couples to schedule sex without planning, and a more spontaneous and natural sexual lifestyle leads to a significant increase in sexual satisfaction for both partners. However, the small dose long-term treatment model raises the financial burden for patients, and for elderly patients or patients with regular sexual ED, some with psychogenic ED, PDE5 inhibitors on-demand still show advantages. In conclusion, PDE5 inhibitors on-demand and low-dose long-term treatment each have their own advantages and cannot replace each other, doctors will choose flexibly according to the specific situation of the patient, individualized treatment.