Twenty-four million Americans use illicit drugs for non-medical reasons and more than 90,000 Americans die every year due to the misuse of alcohol, illicit and prescription drugs. Oral manifestations of drug dependency result from the interplay of direct effects of the drug as well as degradation of oral health due to neglected personal oral hygiene, poor dietary habits, and failure to maintain routine dental visits. The third edition of this Quality Resource Guide (QRG) discusses the current diagnostic criteria for substance abuse, the physiologic and psychological aspects of substance abuse and associated risk factors. It is designed to assist the dentist and his/her staff to recognize oral manifestations of substance abuse as well as provide appropriate oral health care for the substance-abusing patient. It will also assist in development of appropriate office policies and practice strategies to curb and manage inappropriate drug seeking behaviors. Detailed tables will serve as a quick reference before treating patients with substance use disorder. This QRG will serve as an important resource for the dentist, and members of the office staff, as they assess and provide therapy and as a reference when creating appropriate office policies for prescribing medications with abuse potential.