Computer-aided pharmacokinetic, pharmacodynamic, and pharmacokinetic/pharmacodynamic methods are commonly applied to quantify the disposition and the pharmacological effects of the drug, to explore exposure-response relationships, and to predict safety and efficacy outcomes. Use of modeling and simulation throughout the drug development continuum can support more efficient preclinical and clinical study design and interpretation. Mechanism-based approaches where sound biological understanding exists provide meaningful quantitative comparisons between candidates and are sought to support science-based decisions. Simulations from these models allow for scientists to investigate a variety of trial designs where assumptions are clearly stated. The objectives of this review article are to describe commercially available PK/PD software packages and present examples of their application in drug discovery and development. With industry and regulatory support, use of exposure response information may optimize the path to delivery of new medicines to patients. This review is focused on the most common computer software applications in discovery through early development (i.e., GastroPlus, Simcyp Population-based ADME simulator, SAAM II, and WinNonlin), in development (i.e., NONMEM, ADAPT II, MATLAB, WinBUGS, Trial Simulator, and Drug Model Explorer), and across the continuum for data management (i.e., SAS, S-PLUS, and R).