Periodontal disease is an infectious disease. However, certain factors like environmental, physical, social and host stresses may affect and modify disease expression. Certain systemic disorders affecting the neutrophil, monocyte/macrophage and lymphocyte function result in altered production or activity of host inflammatory mediators which may affect the initiation and progression of gingivitis and periodontitis. Evidence has also shed light on the converse side of the relationship between systemic health and oral health i.e. the potential effects of periodontal disease on a wide range of organ systems like the cardiovascular, endocrine, reproductive and the respiratory system. This article sheds light on the effects of periodontal disease on different systemic conditions, the possible mechanisms involved and the role of periodontal therapy on systemic outcomes.