Aminoglycosides are important broad-spectrum antibiotics used in the therapy of many microbial infections. As the bacterial resistance to antibiotic therapy is appearing as an increasingly significant threat to public health, the development of aminoglycoside antibiotics with extended antibacterial spectrum and potency, devoid of nephro- and ototoxicity, and evading the resistance process returns to the focus of researchers. In this review, various developments brought to the aminoglycoside family of antibiotics effective against resistant bacteria have been described, focused on chemical modifications, drug-modifying enzyme inhibitors, and conformationally constrained analogs, as well as related antibacterial compounds, with the hope to provide information useful in rational design of novel antibiotics addressing bacterial resistance, and paving the way for new perspectives in antimicrobial therapy.