In recent years, it has become apparent that the pathogenesis of periodontal diseases is more complex than the presence of virulent microorganisms. In fact, it is now widely accepted that susceptibility to periodontitis varies greatly between individuals who harbor the same pathogenic microflora. To date, the bulk of evidence points to the host response to bacterial challenge as a major determinant of susceptibility. In this review, we will assess the data implicating various inherited and acquired risk factors for susceptibility to periodontal diseases.