Endodontists have the opportunity to apply relevant research findings to the care of their patients using the principles and methods of evidence-based treatment. Finding evidence begins with a specific, well-built clinical question. Once a specific question is framed, the validity and relevance of the evidence need to be appraised. The best levels of evidence can then be used to inform decisions regarding care. The purpose of this paper is to discuss the history of evidence-based treatment and to clarify the process of conducting a systematic review. The various types of research designs appropriate for answering clinical questions most commonly encountered in dental practice, including a description of the strengths and weaknesses of each, are also presented. Finally, the implications of evidence-based research on endodontics and future research are outlined.