Recent advances in medical science, people are living longer and are receiving medical treatment for disorders that were considered to be fatal earlier. Dentistry in today's world is very different from what was practiced about a decade or two ago, not only in methods and procedures but also in the types of patients seen in clinics. The biggest challenge that is faced by any dental clinician is in the assessment and management of patients with complex systemic conditions. Patients who are suffering from medical conditions are frequently encountered in dental practice, presence of symptoms related to the underlying medical diseases, the consequences of systemic disease management, or a combination of both directly impacting dental treatment procedures. While carrying out a procedure in a healthy patient it is only necessary to focus on the course of the treatment, but when it comes to the treatment of a medically compromised patient or any patient having an underlying systemic disease, it is equally important to avoid the potential medical emergencies. Hence, clinician must be aware of common diseases, and drugs that have an impact in endodontic treatment and the management options.