This book constitutes the refereed proceedings of the 12th International Conference on Foundations of Software Science and Computational Structures, FOSSACS 2009, held in York, UK, in March 2009, as part of ETAPS 2009, the European Joint Conferences on Theory and Practice of Software. The 30 revised full papers presented together with two invited talks were carefully reviewed and selected from 102 full paper submissions. The topics addressed are semantics, logics and automata, algebras, automata theory, processes and models, security, probabilistic and quantitative models, synthesis, and program analysis and semantics.