Worldwide vaccination programs against infectious diseases and toxins are estimated to save approximately 3 million lives yearly. Tragically, however, another 3 million individuals (primarily children) die of vaccine-preventable diseases. A significant portion of this problem results from the thermal instability of many of the currently used vaccines. This review argues that modern methods of physical and chemical analysis permit for the first time characterization of the degradative pathways of thermally labile vaccines. A rigorous description of these pathways permit a more rational and systematic approach to the stabilization of vaccines. A direct result of the replacement of currently employed, primarily empirical, approaches to vaccine stabilization with a more molecular-based methodology should be the development of more universally available vaccinations against life-threatening diseases. This has the potential to have a dramatic impact on world health.