Prescription drugs are one of the fastest growing cost components of modern health care systems. Efforts to control escalating costs while simultaneously maximizing population health outcomes have led many countries to implement restrictive criteria on the funding of certain drugs. While drugs are licensed for sale based on evidence of safety and efficacy versus a placebo, many funders now require evidence of clinical- and cost-effectiveness compared to existing drugs as part of their reimbursement criteria. In some countries, concerns about duplication of drug assessment and administrative effort across different jurisdictions have led to experimentation with various forms of centralized drug review processes. Centralized drug reviews strive to standardize, inform, and improve drug reimbursement decisions through critical assessments of comparative clinical- and cost-effectiveness. The ultimate objective is to inform formulary listing decisions that both maximize health outcomes and achieve good "value for money". This paper describes the Common Drug Review (CDR), a uniquely Canadian version of a centralized drug review process, and compares it with the much-studied National Institute for Health and Clinical Excellence (NICE) in the United Kingdom. Through this analysis, which draws on prior critiques and experiences of NICE, we highlight several critical issues for pharmaceutical priority setting that must be considered in the operation and appraisal of centralized drug review processes. These include the selection of drugs for review, centralized versus decentralized decision-making, receptor capacity at local decision making levels, and public participation.