The body defends itself against potentially harmful compounds like drugs, toxic compounds, and their metabolites by elimination, in which the kidney plays an important role. Nephrotoxicity is a major side effect in clinical practice, frequently leading to acute renal failure (ARF); medications may cause renal failure through a variety of mechanisms. Many physiological mechanisms have been implicated in drug-induced renal injury. Tubular nephrotoxicity has been intensively reviewed previously; thus, this review describes the mechanisms of action of several substances (aminoglycoside antibiotics, antifungal agents, immunosuppressive drugs, cancer chemotherapeutic agents, and other toxic substances), all of them acting as glomerular nephrotoxicants.