AbstractThe increased awareness of the central role of RNA has led to realization that RNA, as structural and functional information accumulation, is also drug target to small molecular therapy. Aminoglycosides are a group of well‐known antibiotics, which function through binding to specific sites in prokaryotic ribosomal RNA (rRNA) and affecting the fidelity of protein synthesis. Unfortunately, their clinical practice has been curtailed by toxicity and rapid increasing number of resistant strains. Therefore, it is highly desirable to design new modified aminoglycosides that will overcome the undesirable properties of natural occurring aminoglycosides. On the other hand, aminoglycosides as potential antiviral (HIV) agents were also reported. Herein, we survey the current efforts to develop new aminoglycoside derivatives with modification and reconstruction on each sugar ring and review the latest advances in structure‐activity relationships (SAR). © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 279–316, 2007