This volume contains the papers presented at RECOMB 2010: the 14th Annual International Conference on Research in Computational Molecular Biology held in Lisbon, Portugal, during April 25–28, 2010. The RECOMB conference series was started in 1997 by Sorin Istrail, Pavel Pevzner, and Michael Waterman. RECOMB 2010 was hosted by INESC-ID and Instituto Superior Tecnico, or- nized by a committee chaired by Arlindo Oliveira and took place at the Int- national Fair of Lisbon Meeting Centre. This year, 36 papers were accepted for presentation out of 176 submissions. The papers presented were selected by the Program Committee (PC) assisted by a number of external reviewers. Each paper was reviewed by three members of the PC, or by external reviewers, and there was an extensive Web-based discussion over a period of two weeks, leading to the final decisions. RECOMB 2010 also introduced a Highlights Track, in which six additional presentations by senior authors were chosen from papers published in 2009. The RECOMB conference series is closely as sociated with the Journal of Computational Biology, which traditionally publishes special issues devoted to presenting full versions of selected conference papers.