Drug-related overdoses, and opioid overdoses in particular, have increased substantially over the past two decades, creating a public health crisis. This crisis has hit both urban and rural areas. However, it hit at a time in which rural areas were already struggling to retain population and adjust to new economic realities presented by a transition to service economies and increasing urbanization. Thus, to explore how the opioid crisis may have affected migration and contributed to population loss, we consider countylevel population changes due to all overdose deaths, controlling for other relevant factors, recognizing that opioid overdose is the primary mechanism for overdose death in the United States. We find that higher levels of these deaths in a county are associated with population declines, especially for those aged 25-34, which is problematic since this is the working-age population critical to the long-term economic success in a region. Our findings suggest that policymakers should address the drug crisis, not only to help the affected population, but also as an economic development tool to stop outmigration and to rebuild distressed communities.