This book constitutes the refereed proceedings of the 12th International Conference on Hybrid Systems: Computation and Control, HSCC 2009, held in San Francisco, CA, USA, in April 2009. The 30 revised full papers and 10 revised short papers presented were carefully reviewed and selected from numerous submissions for inclusion in the book. The papers focus on research in embedded reactive systems involving the interplay between symbolic/discrete and continuous dynamical behaviors and feature the latest developments of applications and theoretical advancements in the analysis, design, control, optimization, and implementation of hybrid systems.