Context: The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) created prescription drug coverage for Medicare beneficiaries through a new Part D program, the single largest addition to Medicare since its creation in 1965. Prior to program implementation in January 2006, concerns had been voiced as to how independent pharmacies, which represent a higher proportion of all retail pharmacies in rural areas, would fare under the new program. Purpose: This article describes first-hand reports from rural pharmacist-owners about their experiences with Medicare Part D plans in the first 7 months of 2006 in order to gain a more thorough understanding of the challenges faced by rural independent pharmacies as a result of program implementation. Methods: A semi-structured interview protocol was utilized in telephone interviews with 22 pharmacist-owners of rural independent pharmacies in 10 states. Findings: The rural independent pharmacists interviewed are experiencing major changes in payment, administrative burden, and interaction with patients as a result of the shift of patients into Medicare Part D plans. While administrative burden has greatly increased, payment and clinical interaction have decreased. Conclusion: Actions should be considered that would help rural independent pharmacists adjust to the new circumstances of having Medicare patients mirror, for administrative and payment purposes, commercially insured patients. Long-term modification of existing policies and regulations may be necessary to assure reasonable access to pharmaceuticals for rural populations. Further study is needed to determine how best to target these modifications to essential pharmacies.