Over the past forty years, health care organizations have faced ever-increasing pressures to deliver quality care while facing rising costs, lower reimbursements, and new regulatory demands. Discrete-event simulation has become a popular and effective decision-making tool for the optimal allocation of scarce health care resources to improve patient flow, while minimizing health care delivery costs and increasing patient satisfaction. The proliferation of increasingly sophisticated discrete-event simulation software packages has resulted in a large number of new application opportunities, including more complex implementations. In addition, combined optimization and simulation tools allow decision-makers to quickly determine optimal system configurations, even for complex integrated facilities. This chapter provides an overview of discrete-event simulation modeling applications to health care clinics and integrated health care systems (e.g. hospitals, outpatient clinics, emergency departments, and pharmacies) over the past forty years.