The spondyloarthropathies are diseases influenced by genetic predisposition and, to a varying extent, infectious triggers. A causal role for bacterial infections is most clear for reactive arthritis. Recent insights into arthritogenic components of bacteria may set the stage for a better understanding of disease pathogenesis, the role of heat shock proteins in antigen processing and immune activation, and the adjuvant effect of CpG-DNA. Recent developments in the area of innate immunity broaden current concepts of genetically defined factors in host-pathogen interactions. In particular, the biology of toll-like receptors as important elements in the innate immune response to pathogens is being defined. These factors in innate immunity may have important implications for sequelae of infections, such as reactive arthritis.