In the original SANE Development and Operation Guide, much of the research examined whether registered nurses could perform sexual assault medical forensic examinations. Twenty years later, this revision of the Guide demonstrates that nurses should be the healthcare professionals who provide this care. In the first of five sections the guide defines the SANE as a registered nurse who has completed additional education and training to provide comprehensive health care to survivors of sexual assault. The Guide’s second section provides information on the problem of sexual assault, namely its prevalence, particularly for women, and the resulting trauma for victims that can pervade perceptions of themselves and their social interactions. SANE programs should note which populations are at greater risk for sexual assault and which situations increase the risk of victimization. The Guide’s third section reviews the history and development of SANE programs to show the needs and service gaps that have been addressed by SANE programs. The Guide’s fourth section examines the effectiveness of SANE programs in meeting the needs of sexual assault survivors and assisting law enforcement investigators through the collection of physical evidence that increases the likelihood that sexual assault offenders will be identified and successfully prosecuted. The Guide concludes with a section on building a theoretical framework for SANE practice, which proposes that programs start the SANE development process by acknowledging the importance of incorporating a theory of nursing practice into every aspect of the program.