During recent years, considerable progress has been made in understanding the etiopathogenesis of periodontitis in its various forms and their interactions with the host. Furthermore, a number of reports have highlighted the importance of oral health and disease in systemic conditions, especially cardiovascular diseases and diabetes. In this regard, research has attempted to explain the role of periodontitis in promoting alteration in distant sites and organs. Recently, DNA sequencing studies have revealed how oral infections can occur in distant sites such as the colon, reproductive tissues, metabolic diseases, and atheromas. The objective of this review is to describe and update the emerging evidence and knowledge regarding the association between periodontitis and systemic disease and to analyse the evidence that has reported periodontitis as a risk factor for the development of various forms of systemic diseases in order to provide a better understanding of the possible shared etiopathogenetic pathways between periodontitis and the different forms of systemic diseases.