Nurses are on the front lines of U.S. healthcare, functioning in a variety of healthcare settings, specialties, and environments. Despite the alarming statistics seen from the opioid crisis, nurses can influence safe practices surrounding prescribing and monitoring patients requiring opioid therapy at all levels of prevention. As it is necessary for meeting substance use disorder and addiction challenges seen in the Veteran population, nurses must be aware of physical, psychological, and psychosocial risk factors that may place Veterans at increased risk. It is critical that nurses possess a comprehensive understanding of the role of social determinants of health, or external factors, such as socioeconomic status, education, employment, social support networks, and access to healthcare, which substantially influence health outcomes. Veterans deserve evidence-based competent and compassionate care and nurses must be the ones armed with the necessary knowledge, skills, and attitudes to take on the task of serving and caring for Veterans.