To be effective, antibacterials must be active against microorganism(s) and reach sufficient concentrations at the site of infection. Thus, antibacterial distribution and its subsequent tissue concentration are important determinants of antibiotic efficacy. Tissue distribution has many factors that contribute to an antibiotic reaching the target site of infection. This article reviews those factors (ie, basic biochemical and physiochemical properties of cell membranes, carrier-mediated transporters, plasma- and tissue-protein binding, blood flow, inflammation), and the role of impaired tissue distribution in therapeutic outcomes of patients with a variety of infections. Suboptimal target site concentrations may have important clinical implications in such infections, as they may help explain poor therapeutic outcomes. Therefore, we reviewed and summarized the literature for the concentrations of antibacterials as site to serum ratios, providing practical information as a guide for antibiotic selection.