Phosphodiesterase-5 inhibitors (PDE5i) have been used as the first-line treatment for erectile dysfunction (ED) in recent years. However, with the increased clinical application of PDE5i, the incidence rate of PDE5i-induced adverse reactions is on the rise, which may involve the cardiovascular, digestive, nervous, respiratory, and reproductive systems. Most of the adverse reactions are mild to moderate, occasionally with serious or rare complications. The probability and severity of the adverse reactions are associated with the dosage and frequency of medication as well as with individual differences. Therefore individualized medication is necessitated and, for the patients with cardiovascular disease, epilepsy, psychosis, or anaphylactic conditions, PDE5i should be cautiously given or avoided. This review provides an overview of PDE5i-induced adverse reactions and countermeasures in the treatment of ED.