Recently, there has been a policy momentum toward creating a global tiered pricing framework, which would provide differentiated prices for medicines globally, based on each country's capacity to pay. We studied the most influential proposals for a tiered pricing framework since the 1995 World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights. We synthesized 6 critical questions to be addressed for a global framework to function and explored the many challenges of implementation. Although we acknowledge that there is the potential for an exceptional global commitment that would benefit both producers and those in developing countries in need of wider access to medicines, our greatest concern is to ensure that a global framework does not price out the poor from pharmaceutical markets nor threaten current flexibilities within the international patent regime.