Many advances have been made in the understanding of Crohn’s disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lym-phocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines, chemokines and other mediators produced by a variety of cell types. Prevailing theories of CD pathogenesis suggest that patients’ T-lymphocytes are inappropriately activated in the setting of an immune imbalance, which is itself caused by an unfortunate confluence of genetic and en- vironmental factors. The T-cell response then leads to the chronic inflammation characteristic for the disease. Various environmental factors may play a role in the development of CD, but microbes are most consistently implied. This theory is based on epidemiological, clinico- pathological, genetic and experimental evidence. Despite the abundance of arguments for the implication of bac-teria in the aetiopathogenesis of CD, the precise role of bacteria in this disease still remains elusive. Three not necessarily mutually exclusive theories have been pro- posed: (1) an unidentified persistent pathogen; (2) an abnormally permeable mucosal barrier leading to exces-sive bacterial translocation; and (3) a breakdown in the balance between putative “protective” versus “harmful” intestinal bacteria (“dysbiosis”). At present, one cannot exclude with certainty any of these three proposed hy-potheses; they may all apply to CD to a certain extent. Many advances have been made in the understanding of Crohn’s disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lym-phocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines, chemokines and other Prevailing theories of CD pathogenesis suggest that patients’ T-lymphocytes are inappropriately activated in the setting of an immune imbalance, which is itself caused by unfortunate confluence of genetic and environmental factors. The T -cell response then leads to the chronic inflammation characteristic for the disease. Various environmental factors may play a role in the development of CD, but microbes are most consistently implied. This theory is based on epidemiological, clinico- pathological, genetic and experimental evidence. Despite the abundance of arguments for the implication of bac-teria in the aetiopathogenesis of CD, the precise role of bacteri a in this disease still remains elusive. Three not unpresented exclusive theories have been pro- posed: (1) an unidentified persistent pathogen; (2) an abnormally permeable mucosal barrier leading to exces- sive bacterial translocation; and (3) a breakdown in the balance between putative “protective ” versus “harmful ” intestinal bacteria ( “dysbiosis ”). At present, one can not exclude with certainty any of these three proposed hy-potheses; they may all apply to CD to a certain extent.