BACKGROUND: The Appalachian Research Network (AppNET) was established in the Department of Family Medicine at East Tennessee State University (ETSU) as a network of community primary care preceptors focused on Quality Improvement (QI) in rural Appalachia. As the network has moved forward, following our established aims and priorities to improve the quality of healthcare in rural Appalachia, the importance of transitioning to an interdisciplinary network has emerged. METHOD: AppNET QI projects related to medication reconciliation and prescription drug monitoring led to the development of an AAFP Foundation grant focused on prescription drug abuse/misuse (PDA/M). AppNET approached two ETSU pharmacy faculty experienced in PDA/M research to join the team. Soon after, we were invited to collaborate on an NIH NIDA R-24 submission with the ETSU Bill Gatton College of Pharmacy (GCOP) and the ETSU College of Public Health: Diversity-promoting Institutional Drug Abuse Research Program (DIDARP). This colllaboration has contributed to a variety of AppNET interdisciplinary partnerships resulting in an expanding scope. RESULTS: AppNET’s interdisciplinary partnerships have resulted in several funded projects. In June 2013, we received funding from the AAFP Foundation to assess family physician knowledge, attitudes, and methods for effective and responsible prescribing of pain medication. The ETSU DIDARP grant was awarded in September 2013 with AppNET’s Network Director serving as CoInvestigator on one of three funded projects as well as an AppNET PEA joining the DIDARP team. AppNET is serving as the laboratory for the project, which requires input from providers and pharmacists, leading to the recruitment of pharmacists to the PBRN. In April 2014, through an interdisciplinary partnership of AppNET and GCOP, ETSU was awarded a contract from the Tennessee Department of Health to help combat the Neonatal Abstinence Syndrome (NAS) epidemic in the State. AppNET’s Research Director and a Pharmacy faculty member are leading a project to study the knowledge, attitudes, beliefs, and behaviors of prescribers and dispensers specific to substance use in pregnancy and NAS and evaluate the impact of a NAS primary prevention academic detailing intervention. CONCLUSION: Research in the major health issues facing rural Appalachia, such as PDA/M and NAS, has required an expansion of the research team to include other key professions such as pharmacy and public health. AppNET evolving into an interdisciplinary network has expanded our research scope, our success with obtaining funding, and increased the potential for future funding.