The term host modulation is the alteration of function or status of organism in response to a stimulus or an altered chemical or physical environment. Inflammation is a physiological response to trauma or injury by which the host seeks to remove microorganisms from infected tissues to create favourable condition for tissue healing and restoration of tissue function. Prolonged or excessive inflammatory response of the host damages the tissue and eventually results in the appearance of the disease. Host modulation (with chemotherapeutic agents or drugs) is an adjunctive therapeutic option for the management of periodontal disease. The therapy doesn't block normal defence mechanisms of the host, but alleviates the excessive inflammatory response to enhance the opportunities for wound healing and periodontal stability. The purpose of host modulation therapy is to restore a healthy balance between proinflammatory or destructive mediators and anti-inflammatory or protective mechanisms. Doxycycline at a sub-antimicrobial dose of 20 mg has been indicated as an effective adjunctive method of treating periodontitis which in combination with non-surgical therapy leads to a statistically significant attachment gain and a reduction in probing depth. Periostat® is the only commercially available host modulation agent for the treatment of periodontitis that is administered systemically and is approved by the U.S. Food and Drug Administration (FDA) and American Dental Association (ADA). Further laboratory and clinical research is needed to demonstrate the benefit of using other potentially modulating agents in clinical practice. The development of new host modulating agents will enable the use of additional agents that achieve an improved and predictable host response to non-surgical and surgical therapy of periodontitis.