“Software Tools and Algorithms for Biological Systems" is composed of a collection of papers received in response to an announcement that was widely distributed to academicians and practitioners in the broad area of computational biology and software tools. Also, selected authors of accepted papers of BIOCOMP’09 proceedings (International Conference on Bioinformatics and Computational Biology: July 13-16, 2009; Las Vegas, Nevada, USA) were invited to submit the extended versions of their papers for evaluation.