Community pharmacists frequently encounter patients suspected to be at risk of medication misuse, divergence and overdose; yet, little research exists in describing how pharmacists effectively identify and intervene during these encounters. This study aimed to understand the barriers and facilitators in community pharmacy practice using a focus group design to help inform policymakers in the development of effective and feasible strategies for limiting the means of medication misuse. Findings revealed three themes: (1) patient-level barriers (deciphering signs of misuse); (2) pharmacist-level barriers (type of practice experience); and (3) system-level barriers (prescriber, third-party payer). Insight into pharmacy practice provided a foundation for future study to explore strategies for improving care for at-risk patients.