One factor in deciding whether to undertake a procedure is an awareness of the potential complications and the ability to manage them should they occur.  This advice is applicable to all aspects of clinical dental practice, especially endodontic therapy. This Guide discusses the causes and prevention of complications and then outlines the management of complications should they occur.  The fourth edition of this Guide expands the discussions of obtaining adequate anesthesia in the tooth with symptomatic pulpitis and appropriate use of antibiotics during endodontic therapy.  The Guide’s tables provide a quick reference to treatment options.  Attached to this Guide are the American Association of Endodontists’ Case Difficulty Assessment Form and Guidelines and a form for obtaining informed consent for non-surgical endodontic therapy.