This book constitutes the thoroughly refereed conference proceedings of the 10th International Conference on Computational Methods in Systems Biology, CMSB 2012, held in London, UK, during October 3-5, 2012. The 17 revised full papers and 8 flash posters presented together with the summaries of 3 invited papers were carefully reviewed and selected from 62 submissions. The papers cover the analysis of biological systems, networks, and data ranging from intercellular to multiscale. Topics included high-performance computing, and for the first time papers on synthetic biology.