Sequencing of the entire genome of many species has fuelled the emergence of computational genomics and bioinformatics disciplines. Research in computational genomics uses a combination of sequence analysis, algorithmic and data mining approaches to predict protein function, discover how proteins interact at the cellular level and determine the rules of proteins assembling into different functional networks. This paper is intended to introduce bioinformatics concepts and associated challenges in describing genome functional properties and evolution as well as to illustrate the application of data mining methodologies in large-scale analysis of model organisms. Overall, the progress from individual protein functional assignments to characterisation of entire genomes and functional networks is discussed with the aim to highlight the milestones relating to analysing sequenced genomes as systems. (c) 2007 Published by Elsevier Ltd.