Background: Prescribers and community pharmacists commonly perceive prescription opioid abuse to be a problem in their practice settings and communities. Both cohorts have expressed support for interventions that improve interprofessional communication and reduce prescription opioid abuse. The objective of this study was to describe prescription opioid abuse-related communication among and between prescribers and community pharmacists in South Central Appalachia. Methods: The investigators conducted five focus groups with 35 Appalachian Research Network practice-based research network providers between February and October, 2014. Two prescriber-specific, two pharmacist-specific, and one interprofessional (prescribers and pharmacists) focus groups were conducted, recorded, and transcribed. Data collection and analysis occurred iteratively. Emerging themes were inductively derived and refined. Five member-checking interviews were conducted to validate themes. Results: Providers noted several factors that influence intraprofessional and interprofessional communication, including level of trust, role perceptions, conflict history and avoidance, personal relationships, and prescription monitoring program use. Indirect communication approaches via patients, office staff, and voicemail systems were common. Direct pharmacist to prescriber and prescriber to pharmacist communication was described as rare and often perceived to be ineffective. Prescriber to pharmacist communication was reported by prescribers to have decreased after implementation of state prescription monitoring programs. Difficult or uncomfortable conversations were often avoided by providers. Conclusions: Interprofessional and intraprofessional prescription opioid abuse communication is situational and influenced by multiple factors. Indirect communication and communication avoidance are common. Themes identified in this study can inform development of interventions that improve providers' intra- and interprofessional communication skills.