A focal infection is a localized or generalized infection caused by the dissemination of microorganisms or toxic products from a focus of infection in various organic districts, including the oral district. In the Part 1 of this two-part review article, after historical signs, the Authors describe the current pathogenic concepts like the "immuno-allergic theory" and the formation of auto-antibodies in human body, contributing to the genesis of autoimmune illnesses sustained by individual reactivity linked to eredo-constitutionality. Some theories suppose a focal origin even for general pathology such as cancer, sarcoidosis, multiple sclerosis, amyotrophic lateral sclerosis, autism, Guillain-Barré syndrome, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS), Tourette's syndrome, myasthenia gravis, polycystic kidney disease, obesity, Alzheimer's disease and diabetes mellitus. Laboratory analyses (leucocytic formula, protein electrophoresis, C-reactive protein, REUMA test VES, TAS, etc.) are suggestive of the presence of an inflammatory process or of the presence of an aspecific answer to an inflammatory situation. The DNA-Polymerase Chain Reaction method (PCR) is fundamental for the diagnosis of bacterial and viral infections, particularly for those that have non-culturable microorganisms or in cases where are present but in extremely small number in the sample to be analyzed. A positive result confirms the diagnosis, but negative result is not indicator of the absence of illness. Even for oral inflammatory lesions, different basic mechanisms concerning the possible association with systemic diseases exist. They concern local spread, metastatic spread or immunologic cross-reactivity. In this case we assume that most of the ailments come from dental or periodontal foci, as in the bacterial endocarditis, but instead of considering them as possible pathogenetic mechanism of an immune nature, we consider them as originated by the body's response to the presence of bacterial antigens through the formation of specific antibodies. Much researche, sometimes contrasting, has evaluated periodontal pathogens in atheromatous plaques isolated from patients with chronic periodontitis. Oral inflammatory lesions have been shown unequivocally to contribute to elevated systemic inflammatory responses. In some researches intensive periodontal therapy showed a significant reduction of lymphocyte formula, of CRP levels, of interleukin-6 (IL-6) and of LDL cholesterol after two months.