INTRODUCTION Despite advances in the prevention and treatment of infectious disease, pathogenic bacteria remain the pre-eminent threats to public health worldwide (1). Increasing antibiotic resistance strains and emerging and reemerging infectious agents cause alarming new concerns (2–5). Accordingly, the field of bacterial pathogenesis has rapidly expanded with a greater understanding of pathogenesis at the molecular level over the last decades. The term virulence refers to a quantitative measure of the pathogenicity or the likelihood of a pathogen causing infection (6). However, virulence factors (VFs) apply to the elements (i.e. gene products) that enable a microorganism to colonize a host niche where the organism proliferates and causes tissue damage or systemic inflammation. Conventional VFs include secreted proteins, such as protein toxins and enzymes, and cell-surface structures, such as capsular polysaccharides, lipopolysaccharides and outer membrane proteins, which directly contribute to the disease processes. Now, it becomes clear that many genes encoding virulence traits, such as secretion machineries, siderophores, catalases, regulators, etc. are indirectly involved in pathogenesis, which is equally important for bacteria to establish infection (7). In recent years, rapid progress in bacterial genomic sequencing has led to the discovery and characterization of many new VFs from diverse species, resulting in numerous research papers and reviews each year. This, unfortunately, leads to scattered data at different places, including hard-copy publications as well as many web sites. Obtaining comprehensive information on each of the VFs becomes a formidable task. The virulence factor database (VFDB) reported in this communication is aimed at providing an in-depth coverage of the major VFs from various best-characterized bacterial pathogens, with emphasis on functional and structural biology, and essential immunology. This thorough and comprehensive VFDB will be maintained up to date, which would be helpful for researchers to elucidate pathogenic mechanisms in infectious diseases that require further immediate investigations for the development of novel approaches of the disease treatment and prevention. The currently released VFDB contains cumulative information of VFs for 16 important bacteria pathogens, virulence-associated genes, protein structural features, functions, mechanisms and important literatures. Pathogenicity islands (PAIs), which are clusters of genes encoding virulence traits (8), are also included. Many graphic illustrations are made according to the original research papers or reviews for an easy grasp of the functions and structures of some VFs. The database is user-friendly; fully searchable by query text or by function categories of VFs, as well as by BLAST (9) comparison against all the VF-related genes.