Antibiotics have reduced the mortality from infectious diseases but not the prevalence of these diseases. Use, and often abuse, of antimicrobial agents encourages the evolution of bacteria toward resistance, often resulting in therapeutic failure. This evolution is due to the emergence of "new' resistance mechanisms and to the spread of well-characterized mechanisms of resistance to the majority of bacterial species. Bacterial resistance can be intrinsic or acquired. Intrinsic resistance is species or genus specific and delineates the spectrum of activity of the antibiotic. Acquired resistance is present in only certain strains of a species or of a genus. The latter results from mutation in a gene located in the host chromosome or a plasmid or from acquisition of new genetic information by a bacterium, mainly by conjugation or transformation. In this review, recent developments in the understanding of biochemical mechanisms and the genetics of resistance is considered for the clinically important antibiotic families.