It is currently believed that both the antibacterial potency and the nature of the antibacterial effects of beta-lactam antibiotics are ultimately dependent on the inhibition (acylation) of one or more of the bacterial penicillin-binding proteins (PBPs). Nevertheless, bacterial factors (e.g., autolysins) that do not directly react with the antibiotic molecule also profoundly influence the fate (inhibition of growth or lysis) of the antibiotic-treated bacterial cell. The quantitative relationship between the minimal inhibitory concentration of a beta-lactam antibiotic and its reactivity with certain PBPs is not well understood. Also poorly understood is the mechanism by which inhibition of PBP function causes triggering of suicidal autolytic activity. Much remains to be done before the structural basis of the highly selective PBP affinities observed with some beta-lactam antibiotics is understood. A new form of antibiotic resistance involving mutational alteration of PBPs (in the direction of lower antibiotic affinity) has emerged among clinical isolates of most of the major human pathogens.