The focal infection theory was prominent in the medical literature during the early 1900s and curtailed the progress of endodontics. This theory proposed that microorganisms, or their toxins, arising from a focus of circumscribed infection within a tissue could disseminate systemically, resulting in the initiation or exacerbation of systemic illness or the damage of a distant tissue site. For example, during the focal infection era rheumatoid arthritis (RA) was identified as having a close relationship with dental health. The theory was eventually discredited because there was only anecdotal evidence to support its claims and few scientifically controlled studies. There has been a renewed interest in the influence that foci of infection within the oral tissues may have on general health. Some current research suggests a possible relationship between dental health and cardiovascular disease and published case reports have cited dental sources as causes for several systemic illnesses. Improved laboratory procedures employing sophisticated molecular biological techniques and enhanced culturing techniques have allowed researchers to confirm that bacteria recovered from the peripheral blood during root canal treatment originated in the root canal. It has been suggested that the bacteraemia, or the associated bacterial endotoxins, subsequent to root canal treatment, may cause potential systemic complications. Further research is required, however, using current sampling and laboratory methods from scientifically controlled population groups to determine if a significant relationship between general health and periradicular infection exists.