The5th editionof the InternationalSymposium onBioinformaticsResearchand Applications (ISBRA 2009) was held during May 13-16, 2009 at Nova Sou- eastern University in Ft. Lauderdale, Florida. The symposium provides a forum for the exchange of ideas and results among researchers, developers, and prac- tioners working on all aspects of bioinformatics and computational biology and their applications. The technical program of the symposium included 26 contributed papers, selected by the Program Committee from a number of 55 full submissions - ceived in response to the call for papers. The technical program also included contributed papers and abstracts submitted to the Second Workshop on C- putational Issues in Genetic Epidemiology (CIGE 2009), which was held in c- junction with ISBRA 2009. Additionally, the symposium included poster s- sions and featured invited keynote talks by four distinguished speakers: Mikhail Gelfand from the Russian Academy of Sciences and Moscow State University spoke on evolution of regulatory systems in bacteria, Nicholas Tsinoremas from the Miller School of Medicine and the College of Arts and Sciences at the U- versity of Miami spoke on bioinformatics challenges in translational research, Esko Ukkonen from the University of Helsinki spoke on motif construction from high-throughputSELEXdata, andShamil SunyaevfromBrighamand Women's Hospital and Harvard Medical School spoke on interpreting population seque- ing data. We would like to thank the Program Committee members and external - viewers for volunteering their time to review and discuss symposium papers.