<p>Like many other body structures, the mouth is often affected by disease that principally arises from, or targets, several tissue sites. Indeed, systemic disorders can manifest on the oral mucosa as the first, only, or become the most severe manifestation of a systemic disease and/or become the most significant factor to adversely affect an individual's quality of life. Oral healthcare providers (dentists, therapists and hygienists) may be the first to observe an abnormality in the mouth which sometimes indicates a significant systemic disease unknown to the patient or their general medical practitioner. The role of the majority of oral healthcare providers is not necessarily to determine the diagnosis but to take appropriate actions when there is a possible abnormality, as this can, and often will, make a positive difference to the patient and indeed, those around them.</p><p>The aim of the present article is to provide a succinct review of the oral features of early systemic disease. There is no intention to discuss every possible scenario but to present the most likely and demonstrate the wide range of disease processes that may impact upon the mouth. The article does not consider the early orofacial features of systemic drug therapy, as while this is an area of immense change, it falls outside the scope of the present review.</p>