This volume contains the papers presented at the 10th Annual International Conference on Research in Computational Molecular Biology (RECOMB 2006), which was held in Venice, Italy, on April 2-5, 2006. The RECOMB conference serieswasstartedin1997bySorinIstrail,PavelPevznerandMichaelWaterman. The table on p. VIII summarizes the history of the meetings. RECOMB 2006 was hosted by the University of Padova at the Cinema Palace of the Venice Convention Center, Venice Lido, Italy. It was organized by a committee chaired by Concettina Guerra. A special 10th Anniversary Program Committee was formed, by including the members of the Steering Committee and inviting all Chairs of past editions. The Program Committee consisted of the 38 members whose names are listed on a separate page. From212submissionsofhighquality,40paperswereselectedforpresentation atthemeeting,andtheyappearintheseproceedings.Theselectionwasbasedon reviewsandevaluationsproducedbytheProgramCommitteemembersaswellas byexternalreviewers,andonasubsequentWeb-basedPCopenforum.Following thedecisionmadein2005bytheSteeringCommittee,RECOMBProceedingsare published as a volume of Lecture Notes in Bioinformatics (LNBI), which is - editedbythefoundersofRECOMB. Traditionally,theJournalofComputational Biology devotes a special issue to the publication of archival versions of selected conference papers. RECOMB 2006 featured seven keynote addresses by as many invited spe- ers: Anne-Claude Gavin (EMBL, Heidelberg, Germany), David Haussler (U- versity of California, Santa Cruz, USA), Ajay K. Royyuru (IBM T.J. Watson ResearchCenter, USA), David Sanko? (University of Ottawa,Canada), Michael S. Waterman (University of Southern California, USA), Carl Zimmer (Science Writer, USA), Roman A. Zubarev (Uppsala University, Sweden). The Stanislaw Ulam Memorial Computational BiologyLecture was given by Michael S. Wat- man. A special feature presentation was devoted to the 10th anniversary and is included in this volume.