Microbial foes have the advantage of an extraordinary capacity to rapidly reproduce and adapt, thereby propagating themselves even in the face of impressive advances in public health and the availability of countermeasures such as diagnostics, therapeutics, and vaccines. This inherent adaptability of microbes can only be matched with the continual application of wit and technological capability. The best defense for the human species against elimination by the ever-evolving waves of microbial pathogens are public health measures coordinated with biomedical research that will continue to provide innovative tools to counterbalance these endless microbial challenges. Ultimately, if medical science continues to fight the microbial foes to a draw, as has occurred for much of the past century, humanity will have won.