The COVID-19 pandemic created a number of rapidly emerging and unprecedented challenges for those engaged in substance use disorder (SUD) treatment, forcing service providers to improvise their treatment strategies as the crisis deepened. Drawing from five ongoing federally funded SUD projects in Appalachian Tennessee and hundreds of hours of meetings and interviews, this article explores the pandemic's impact on an already structurally disadvantaged region, its recovery community, and those who serve it. More specifically, we note detrimental effects of increased isolation since the implementation of COVID-19 safety measures, including stakeholders' reports of higher incidences of relapse, overdose, and deaths in the SUD population. Treatment providers have responded with telehealth services, but faced barriers in technology access and computer literacy among clients. Providers have also had to restrict new clients to accommodate social distancing, faced delays in health screening those they can accept, and denied family visitations, which has affected retention. In light of these challenges, several promising lessons for the future emerged––such as preparing for an influx of new and returning clients in need of SUD treatment; making arrangements for long-term housing and facility modification; developing a hybrid care delivery model, taking advantage of new regulations enabling telemedicine; budgeting for and storing personal protective equipment (PPE) and related supplies; and developing disaster protocols to withstand threats to intake, retention, and financial solvency.