The practice of dentistry requires an understanding of medical illnesses and the implications of treatment on the oral environment. Periodic review enables the practitioner to anticipate patient needs and to interact competently with other medical care providers. Presented in this review are recent advances in understanding the relationship between medical and oral diseases. Where appropriate, therapeutic regimens for the treatment of oral manifestations are suggested. Diabetes remains equivocally associated with periodontal disease. The dynamic nature of the immune system and the exhaustive list of oral microbial flora have led to immense and promising research in understanding the pathogenesis of periodontal diseases. It is anticipated that this would lead to methodologies that could modulate the mechanisms of host response and thereby regulate, for example, bone resorption in inflammatory periodontal diseases. HIV-associated periodontal and other oral manifestations have provoked challenging goals in efficient treatment of these patients. The survival time of cancer patients continues to lengthen, resulting in significant numbers of affected individuals. Treatment modalities, chiefly radiation and chemotherapy, produce marked effects on the oral tissues. The detrimental oral consequences of oncologic therapy can be reduced with proper patient education and attention to prophylactic measures. Neoplasia occurs within the oral environment often mimicking inflammatory disease. Systemic diseases may manifest orally and may be subtle in presentation. The dentist is compelled to evaluate all lesions of the oral tissues with the expectation that they may be a lesser sign of a more severe condition.