The anatomic localization and unique vasculature of the liver, along with its cell properties, make this organ an efficient line of defense against blood-borne infections, either systemic or arising in the abdomen. Liver cells can modify the host immune response by releasing immunomodulatory molecules, interacting with cells of the immune system and acting as scavengers for inflammatory mediators. However, these defensive functions do not protect the liver itself from the severe injury that may be caused by pathogens, toxins or pollutant xenobiotics. Therefore, the mammalian liver has developed a unique adaptation in the form of an astonishing regenerative capability. The complexity of regeneration requires a well-orchestrated system to control this process. Growing evidence suggest the importance of immune mechanisms as a part of this system. It seems likely that the mechanisms that serve to eliminate infections (and may simultaneously cause liver injury) are also active in restoring the structural and functional integrity of the damaged liver.