This book constitutes the refereed proceedings of the 12th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2008, held in Singapore, in March/April 2008. The 34 revised full papers presented together with the abstracts of 7 keynote talks were carefully reviewed and selected from 193 submissions. As the top conference in computational molecular biology, RECOMB addresses all current issues in algorithmic, theoretical, and experimental bioinformatics such as molecular sequence analysis, recognition of genes and regulatory elements, molecular evolution, protein structure, structural genomics, gene expression, gene networks, drug design, combinatorial libraries, computational proteomics, as well as structural and functional genomics.