Testing for systemic diseases in dental clinics is a potentially attractive avenue for oral health professionals and may be viewed as an opportunity to increase professional reach, expand practice, and improve financial returns. However, several ethical questions arise that must be addressed before such activities are adopted. (1) What should be the level of training dentists must acquire to deal with challenges associated with testing? (2) How well are dental practices aware of and compliant with the Health Insurance Portability and Accountability Act and procedures related to informed consent? (3) What is the evidence regarding acceptability and effectiveness of testing? (4) What should be the acceptable standard of practice for conduct of invasive and noninvasive tests? (5) What is the boundary delineating “testing” and “reporting” vis-à-vis counseling? (6) What is the value of testing without counseling? (7) What assurances need to be in place to ensure voluntariness of testing? (8) How would data from testing be used in “research,” especially with the growth of practice based research networks? and (9) Does the American Dental Association Code of Ethics need to incorporate guidance for practicing dentists? We discuss how ethical principles can be used to develop a framework of guidelines for potential testing for systemic diseases in dental clinics..