The kidneys are vital organs that play an important role in removing waste materials from the blood, electrolyte balance, blood pressure regulation, and red blood cell genesis. Kidney disease can be caused by various factors, including diabetes, ischemia/reperfusion injury, and nephrotoxic agents. Inflammation and oxidative stress play a key role in the progression and pathogenesis of kidney diseases. Acute kidney injury (AKI) and chronic kidney disease (CKD) are important health problems worldwide, as they are associated with a long-term hospital stay, and increased morbidity and mortality in high-risk patients. Current standard therapeutic options are not sufficient to delay or stop the loss of kidney function. Therefore, it is necessary to develop new therapeutic options. Phosphodiesterase 5 inhibitors (PDE5Is) are a currently available class of drugs that are used to treat erectile dysfunction and pulmonary hypertension in humans. However, recent evidence suggests that PDE5Is have beneficial renoprotective effects via a variety of mechanisms. In this review, the benefits of PDE5 inhibitors in clinical conditions associated with kidney disease, such as diabetic nephropathy, ischemia-reperfusion injury, and acute and chronic kidney injury, are summarized.