The LNCS journal Transactions on Computational Systems Biology is devoted to inter- and multidisciplinary research in the fields of computer science and life sciences and supports a paradigmatic shift in the techniques from computer and information science to cope with the new challenges arising from the systems-oriented point of view of biological phenomena. This, the third Transactions on Computational Systems Biology volume, edited by Emanuela Merelli, Pedro Pablo Gonzalez and Andrea Omicini, is devoted to considerably extended versions of selected papers presented at the International Workshop on Network Tools and Applications in Biology (NETTAB 2004), held at the University of Camerino, in Camerino, Italy, in September 2004. Dedicated especially to models and metaphors from biology to bioinformatics tools, the 10 papers selected for the special issue cover a wide range of bioinformatics research such as data visualisation, protein/RNA structure prediction, motif finding, modelling and simulation of protein interaction, genetic linkage analysis, and notations and models for systems biology.