Tenofovir is a reverse-transcriptase inhibitor based on acyclic nucleotide analogs. Tenofovir is a drug that is often used in treating HIV infection and has also been approved for treating infection by the hepatitis B virus. Despite the fact that its renal safety has been demonstrated in cell culture and clinical trials, clinical use and in vivo animal studies have shown its association with a low, but important, risk of kidney injury. Tenofovir accumulation in these mitochondria-rich cells is explained by proximal tubular cell secretion. Proximal tubular cell dysfunction is a symptom of Tenofovir nephrotoxicity, which might be the leading cause of acute renal injury or chronic diseases of the kidney. A review of articles is performed using keywords related to the topic in the databases of Google Scholar and PubMed, and 54 papers have been included, which were case studies, crosssectional studies, and in vivo animal studies from 2004 up to 2021. The review aims at explaining the interaction of Tenofovir with kidney tubules, an association of genetic polymorphism, clinical features of Tenofovir-induced renal toxicity, potential mechanisms of Tenofovir-induced renal toxicity, its predisposing conditions and factors, and finally, some proposed strategies and agents to monitor and manage Tenofovir-induced nephrotoxicity.