Cost containment in health care services is becoming more and more important in a context in which the demand for health care services is increasing because of the population ageing (from 4 % in 2010 to nearly 10 % in 2050 in OECD countries), the increase in chronic pathologies and the social changes over recent decades. The way in which health care service organizations are managed affects their global system performance and needs to be re-designed in order to address the requirements of the new environment.The primary objective of this Special Issue is to publish papers that reflect recent developments to improve the service delivery in health care systems. Scientists and practitioners presented their current research topics at the International Conference on Health Care Systems Engineering (HCSE) 2013 held in Milano, Italy, at San Raffaele Hospital in the areas of health care systems modeling, simulation, and optimization. All of the contributions selected in this Special Issue propose novel methods, models and analyses illustrated by real world examples.