Introduction: Aminoglycosides are of the oldest antibiotics. Even though representatives of the class are used in various applications, the use that has established aminoglycosides in medicine is their antimicrobial activity.

Areas covered: Current knowledge on mechanism of action, adverse events, strategies to overcome toxicity and increase efficacy of aminoglycosides, as well as therapeutic uses and future perspectives of this class of antibiotics.

Expert opinion: Aminoglycosides are still the treatment of choice for diseases such as brucellosis and plague. Toxicity, along with the discovery of equally potent and less toxic antibiotics, has shelved aminoglycosides the past 30 years. However, this has largely saved them from resistance development. Apart from retaining efficacy, strategies to overcome toxicity, especially once daily administration, has made aminoglycosides a safer choice. Further, plazomicin is a very promising synthetic aminoglycoside that escapes all clinically significant aminoglycoside-modifying enzymes and has completed a clinical Phase II trial. Despite being in clinical practice for > 60 years, issues such as the synergistic role of aminoglycosides in Gram-positive endocarditis remain controversial. Prospective randomized trials are needed to clarify the benefit of aminoglycosides in this setting. Nonetheless, in an era of emerging resistance, aminoglycosides are valuable weapons against multidrug-resistant pathogens.