Antibiotics are the leading cause of drug-induced kidney disease, and among them the aminoglycosides (AMG) are the main nephrotoxic agents, bringing about kidney damage via a direct dose-dependent mechanism. The combination of an aminoglycoside and a penicillin derivative is still the most commonly recommended and used first-line treatment modality in the empirical therapy of neonatal sepsis, despite the low therapeutic index of AMG. The immaturity of neonatal kidney function, particularly in preterm neonates, makes newborn infants particularly susceptible to AMG-induced kidney damage. Numerous factors intervene in bringing about AMG-induced kidney damage, such as factors related to the antibiotic itself (intrinsic toxicity, administration route, type of monitoring of blood concentrations), those related to the subject treated (neonatal age, constitutional sensitivity), and others related to associated pathology (neonatal anoxia, renal hypoperfusion, respiratory distress/mechanical ventilation, hyperbilirubinaemia/phototherapy, electrolyte disorders, and even the acute sepsis calling for antibiotic therapy), as well as pharmacological factors (concomitant therapies such as diuretics, indomethacin and other antibiotics, particularly glycopeptides and cephalosporins).