This book constitutes the refereed proceedings of the International Conference on Computational Methods in Systems Biology, CMSB 2006, held in Trento, Italy, in October 2006.The 22 revised full papers presented together with 2 invited talks were carefully reviewed and selected from 68 submissions. The papers present a variety of techniques from computer science, such as language design, concurrency theory, software engineering, and formal methods, for biologists, physicists, and mathematicians interested in the systems-level understanding of cellular processes.