This volume contains the proceedings of the 6th Conference on Computational Methods in Systems Biology (CMSB) held in October 2008 in Rostock/ Warnemunde. ] The CMSB conference series was established in 2003 to promote the c- vergence of (1) modelers, physicists, mathematicians, and theoretical computer scientists from ?elds such as language design, concurrency theory, software ve- ?cation, and (2) molecular biologists, physicians, neuroscientists joined by their interest in a systems-level understanding of cellular physiology and pathology. Sincethistime, theconferencehastakenplaceannually. Theconferencehasbeen held in Italy, France, and the UK, and we were glad to host CMSB in Germany for the ?rst time. The summaries of the invited talks by Hidde de Jong, Jane Hillston, Koichi Takahashi, Nicolas Le Novere, and Dieter Oesterhelt are included at the - ginning of the proceedings. The 21 regular papers cover theoretical or applied contributions that are motivated by a biological question focusing on modeling approaches, including process algebra, simulation approaches, analysis methods, in particular model checking and ?ux analysis, and case studies. They were - lected out of more than 60 submissions by a careful reviewing process. Each paper received at least three reviews from members of the Program Committee consistingof27renownedscientistsfromsevencountries. We wouldliketothank all members of the Program Committee and the referees for the thorough and insightful reviews and the constructive discussions. Due to the number of hi- quality submissions, the decision on which papers to accept or reject was not easy. Therefore, we integrated a rebuttal phase for the ?rst tim