The four-volume set LNCS 3991-3994 constitutes the refereed proceedings of the 6th International Conference on Computational Science, ICCS 2006, held in Reading, UK, in May 2006. The main conference and its 32 topical workshops attracted over 1400 submissions. The 98 revised full papers and 29 revised poster papers of the main track presented together with 500 accepted workshop papers were carefully reviewed and selected for inclusion in the four volumes. The papers span the whole range of computational science, with focus on the following major themes: tackling grand challenges problems; modelling and simulations of complex systems; scalable algorithms and tools and environments for computational science. Of particular interest were the following major recent developments in novel methods and modelling of complex systems for diverse areas of science, scalable scientific algorithms, advanced software tools, computational grids, advanced numerical methods, and novel application areas where the above novel models, algorithms and tools can be efficiently applied such as physical systems, computational and systems biology, environmental systems, finance, and others.