This analysis of in-depth interviews captures perceptions by first responder agencies working on the front lines of the opioid and other drug crises in some of the nation’s hardest-hit communities. Its purpose was to gain insights into the needs of the first responder workforce in response to staff members’ exposure to potentially traumatic stressors. It describes how overdose response duties affect individuals and organizations, the measures agencies take to minimize any negative consequences, and suggestions on ways to better prepare and support the field to manage the associated stressors.