The experience of COVID-19 has recently confirmed the image of vaccines as a holy grail of disease control. Despite this technology’s track record in successfully preventing various diseases, not all pathogens are as easily neutralized through vaccination as those for smallpox, polio, or COVID-19. Scientists have spent decades and billions in research funding trying to develop vaccines for HIV/AIDS, tuberculosis, and malaria and still lack the kind of “magic bullet” initially hoped for. Using the malaria vaccine as a case study, this project examines the history of vaccines that have thus far failed to live up to their promise to address some of the world’s most widespread and deadliest diseases. Additionally, it considers the consequences of the stalled, slow, ongoing efforts to research and develop such tools for scientific knowledge, scientists and their institutions, disease control funding and approaches, and the populations intended to benefit from these biomedical promises.