The two volume set LNCS 6415 and LNCS 6416 constitutes the refereed proceedings of the 4th International Symposium on Leveraging Applications of Formal Methods, ISoLA 2010, held in Heraklion, Crete, Greece, in October 2010. The 100 revised full papers presented were carefully revised and selected from numerous submissions and discuss issues related to the adoption and use of rigorous tools and methods for the specification, analysis, verification, certification, construction, test, and maintenance of systems. The 46 papers of the first volume are organized in topical sections on new challenges in the development of critical embedded systems, formal languages and methods for designing and verifying complex embedded systems, worst-case traversal time (WCTT), tools in scientific workflow composition, emerging services and technologies for a converging telecommunications / Web world in smart environments of the internet of things, Web science, model transformation and analysis for industrial scale validation, and learning techniques for software verification and validation. The second volume presents 54 papers addressing the following topics: EternalS: mission and roadmap, formal methods in model-driven development for service-oriented and cloud computing, quantitative verification in practice, CONNECT: status and plans, certification of software-driven medical devices, modeling and formalizing industrial software for verification, validation and certification, and resource and timing analysis.