This article briefly introduces and discusses main roles of phosphodiesterase type 5 inhibitors (PDE5i), single and combination treatment, and its long-term tolerability in patients with cardiovascular disease (coronary artery disease) beyond erectile dysfunction. At the same time, the author comments the Mendelian randomization (MR) analysis on PDE5i for ischemic heart disease and mortality in a recent study, as well as anti-tumor functions and applications of PDE5i in cancers, and other clinical uses, particularly combining with healthy lifestyle.