In 2002 the U.S. National Science Foundation created a Blue-Ribbon Advisory Panel on Cyberinfrastructure, which submitted in January of 2003 a report entitled “Revolutionizing Science and Engineering Through Cyberinfrastructure.” Subsequently, the NSF created an Office of Cyberinfrastructure (OCI) independent of its directorates in such traditional areas as biology, computer science, geosciences, physical science, and engineering. In the following 3 years the NSF sponsored workshops leading to nearly 30 reports (www.nsf.gov/od/oci/reports.jsp) on the role of cyberinfrastructure in specific areas of research. This chapter describes a variety of projects that fall into the intersection of cyberinfrastructure with the study and practice of large-scale optimization. In general, these projects involve large-scale optimization problems in system design, production planning, and logistics. However, the notion of large-scale optimization occurs in other disciplines including physical and biological sciences, engineering, economics. As such, there is a benefit to establish a community whose members use the same modeling and algorithmic techniques and who can benefit from the same software and services.