The clinical outcome of anti-infective treatment is determined by both PK and PD properties of the antibiotic. Only the free tissue concentrations of antibiotics at the target site, which are usually lower than the total plasma concentrations, are responsible for therapeutic effect. The free antibiotic concentrations at the site of action are a more appropriate PK input value for PK-PD analysis. The unbound tissue concentrations can be measured directly by microdialysis. Using plasma concentrations overestimates the target site concentrations and its clinical efficacy. The optimal dosing regimens of antibiotics have an impact on patients' outcome and cost of therapy, and reduce the emergence of resistance.