Aminoglycosides have long been one of the commonest causes of drug-induced nephrotoxicity (137). Although a clear recognition of the patient-and treatment-related risk factors (91), combined with the once-a-day schedule and effective monitoring procedures (98), have definitely improved the situation over what prevailed in the early 1980s (115), we are still short of having brought the safety of aminoglycosides to that of the main other wide-spectrum antibiotics. Chemical research aimed at obtaining intrinsically less toxic compounds has met with only modest success, and few of the other approaches proposed to reduce the toxicities of the available agents have reached practical clinical applications. Yet, because aminoglycosides are very effective antibiotics well suited to the treatment of severe infections (35), it seems important to maintain and even develop efforts to improve their therapeutic indices. The present minireview tries to present in a prospective way the status of both the basic and the clinical research on aminoglycoside nephrotoxicity in order to clarify the main issues and to pinpoint strategies that may eventually lead to their safer use. Ototoxicity, which is the second main adverse effect of aminoglycosides and which, in contrast to nephrotoxicity, is irreversible, will not be considered here since it has already been reviewed in this journal (52) and elsewhere (10). A companion minireview (83) examines and discusses the recent research dealing with the activities of aminoglycosides and bacterial resistance.