This book constitutes the refereed proceedings of the First International Conference on Computational Systems-Biology and Bioinformatics, CSBio 2010, held in Bangkok, Thailand, in November 2010. The 19 revised full papers presented were carefully reviewed and selected from a total of 48 submissions. The papers cover a wide range of topics and are organized in five topical sections on modeling and simulation of biological processes, gene expression analysis, biological sequence analysis and network reconstruction, bio-data visualization and biological databases, as well as medical and biomedical informatics.