Several lines of evidence support the causative role of oral inflammatory lesions and certain systemic diseases, such as atherosclerosis and cardiovascular diseases, adverse pregnancy outcome and lung diseases. Properly executed epidemiologic studies identified increased odds ratios. Local or metastatic spread of oral microorganisms, local production of microbial or host-derived soluble regulatory molecules, that may initiate or sustain inflammatory events in remote tissues and organs and the presence of (a) common – extrinsic- or intrinsic-pathological mechanism(s) may result in or contribute to both local and systemic inflammation. A number of cross-sectional studies addressing a possible association between oral health and systemic diseases have also investigated the presence or the absence of periapical lesions. However, these studies cannot either confirm or refute a role of the periapical inflammatory lesion in the observed associations, since other variables of oral health might have exerted an inestimable influence on general health of the assessed population. The literature, dealing with patients with root canal infections and apical periodontitis as sole oral inflammatory lesions is extremely sparse. Our group has demonstrated that young adults with apical periodontitis exhibit certain biochemical changes, such as elevated levels of C-reactive protein and an increased whole blood chemiluminescence, which have been shown to elevate the risk for cardiovascular diseases. Future research will be required to determine whether and to what extent may endodontic diseases affect general health.