Periodontitis is now seen as resulting from a complex interplay of bacterial infection and host response, often modified by behavioral factors. There has been a fundamental change in the prevailing periodontal disease model of the 1960s, which suggested that the susceptibility to periodontitis increases with age, and that all individuals are susceptible to severe periodontal disease. More recent research has changed the belief in universal susceptibility to the current view that only some 5-20% of any population suffer from severe generalized periodontitis, and that only moderate disease affects a majority of adults. One major risk factor is smoking, as there is now a clear association between smoking and periodontal disease independent of oral hygiene, age, or any other risk factor. In human periodontitis, there is no simple, direct pathogen-disease link. There are three pathogens that have a strong association with progressive periodontal disease: Actinobacillus actinomycetemcomitans, spirochetes of acute necrotizing gingivitis, and Porphyromonas gingivalis. These pathogens may be the cause of continued loss of periodontal attachment in all periodontal disease classifications despite diligent periodontal therapy. This loss of attachment, or destruction of the periodontal ligament and loss of adjacent supporting bone, is seen in adult periodontitis, as well as in early-onset periodontitis, which affects young persons who otherwise appear healthy. The three forms of early-onset periodontitis are prepubertal periodontitis, localized and generalized juvenile periodontitis, and rapidly progressive periodontitis. They are distinguished from adult periodontitis by the age of onset of the disease, the rapid rate of disease progression, manifestations of defects in host response, and the composition of the subgingival microflora. Prepubertal periodontitis is associated with attachment loss around teeth of the deciduous and/or permanent dentition, and is often associated with severe congenital defects of hematological origin, and alterations in neutrophil chemotaxis function. Periodontitis may also be associated with systemic conditions such as metabolic disorders (diabetes mellitus, female hormonal alterations), drug-induced disorders, hematologic disorders/leukemia, and immune system disorders. These systemic disorders have been documented as capable of affecting the periodontium and/or treatment of periodontal disease. In order to rationally treat and prevent periodontal disease, we need to know the etiologic agents for specific patients, and the mechanism of bacterial pathogenesis in periodontitis. In systemic diseases in which the periodontal tissues are affected as well, early detection and carefully managed therapeutics with the physician and periodontist working together may prove beneficial to the patient's general health and quality of life.