Appropriate treatment with antimicrobials involves factors we cannot control. Factors such as interpatient variability in drug exposure, the minimum inhibitory concentration (MIC) of the infecting pathogen, and the patient's clinical status clearly affect the therapeutic response. Despite these uncertainties, we can estimate the probability of attaining a successful therapeutic outcome in the context of factors that are within our control. Chief among these are drug, dose, and the dosing interval. One way to predict the probability of a positive therapeutic outcome is through the use of an integrated pharmacokinetic-pharmacodynamic stochastic model. Pharmacokinetic-pharmacodynamic target attainment analyses using Monte Carlo simulation to integrate interpatient variability in drug exposure, drug potency, and in vivo exposure targets predictive of positive therapeutic outcomes are influencing antibacterial susceptibility breakpoints at home and abroad. The consequences of this paradigm shift are far reaching, affecting the commercial concerns of drug and susceptibility testing device manufacturers, perceptions about antimicrobial resistance, and ultimately patient care decisions.