Developing and distributing a safe and effective SARS-CoV-2 (COVID-19) vaccine has garnered immense global interest . Less than a year after COVID-19 was declared a pandemic, several vaccine candidates had received emergency use authorization across a range of countries . Despite this scientific breakthrough, the journey from vaccine discovery to global herd immunity against COVID-19 continues to present significant policy challenges that require a collaborative, global response . We offer a framework for understanding remaining and new policy challenges for successful global vaccine campaigns against COVID-19 as well as potential solutions to address them . Decision-makers must be aware of these challenges and strategize solutions that can be implemented at scale . These include challenges around maintaining R & D incentives, running clinical trials, authorizations, post-market surveillance, manufacturing and supply, global dissemination, allocation, uptake, and clinical system adaption . Alongside these challenges, financial and ethical concerns must also be addressed.