Resistant bacteria have renewed our interest in the aminoglycoside drugs. Evidence on the efficiency of aminoglycosides in their different clinical uses is available from numerous randomized controlled trials and has been accrued and examined in recent systematic reviews and meta-analyses. Their results show that aminoglycosides should not be added to broad-spectrum beta-lactams to achieve synergism in treating Gram-negative infections as combination does not improve efficacy and adds side effects. The evidence from randomized trials in humans does not support the use of aminoglycosides in staphylococcal or streptococcal endocarditis, and is lacking for endocarditis caused by enterococci. Aminoglycosides are efficacious and safe as single drugs for the treatment of pyelonephritis and sepsis of a urinary source, but their efficacy might be lower than that of beta-lactams in Gram-negative infections of other sources. In patients with no risk factors, aminoglycosides are as safe as beta-lactams regarding side effects. They probably induce less resistance. Pragmatic large trials are needed to answer open clinical questions on the use of aminoglycosides.