This volume contains the conference proceedings of the 4th International S- posium on Leveraging Applications of Formal Methods, Veri?cation and Vali- tion, ISoLA 2010, which was held in Greece (Heraklion, Crete) October 18–21, 2010, and sponsored by EASST. Following the tradition of its forerunners in 2004, 2006, and 2008 in Cyprus and Chalchidiki, and the ISoLA Workshops in Greenbelt (USA) in 2005, in Poitiers (France) in 2007, and in Potsdam (Germany) in 2009, ISoLA 2010 p- vided a forum for developers, users, and researchers to discuss issues related to the adoption and use of rigorous tools and methods for the speci?cation, ana- sis, veri?cation, certi?cation, construction, testing, and maintenance of systems from the point of view of their di?erent application domains. Thus, the ISoLA series of events serves the purpose of bridging the gap between designers and developers of rigorous tools, and users in engineering and in other disciplines, and to foster and exploit synergetic relationships among scientists, engineers, software developers, decision makers, and other critical thinkers in companies and organizations. In particular, by providing a venue for the discussion of c- mon problems, requirements, algorithms, methodologies, and practices, ISoLA aims at supporting researchers in their quest to improve the utility, reliability, ?exibility, and e?ciency of tools for building systems, and users in their search for adequate solutions to their problems.