Regarding climate change, there is a specific concern about new diseases from the fungal kingdom (6). The endothermy pillar is robust in humans, but it can be defeated if the fungi adapt to higher temperatures. Although most fungal species cannot tolerate mammalian temperatures (4), some species can be trained to survive higher temperatures by gradual exposure to warmer temperatures. Hence, we have proposed that global warming will lead many fungal species to adapt to higher temperatures, and some with pathogenic potential for humans will break through the thermal defensive barrier provided by endothermy (6). The nearly simultaneous emergence of Candida auris on three continents (7), an event proposed to result from global warming (8), has raised the specter that increased warmth by itself will trigger adaptations on certain microbes to make them pathogenic for humans. Fungi that are pathogenic for insects can be experimentally adapted to replicate at mammalian temperatures through cycles of progressive warming, demonstrating that fungi are able to adapt rapidly to higher temperatures (9). If these threats materialize, medicine will need to confront new infectious diseases for which it has no experience. Although the experience with Lyme disease, HIV, SARS coronaviruses, Zika virus, and C. auris shows that medicine and science can eventually respond successfully to previously unknown microbes with new diagnostics, control measures, and therapeutics, effective responses take time, and countless lives are lost in the meantime. However, various measures could be taken today to increase preparedness for confronting new infectious diseases. Enhance surveillance for new diseases. Designing enhanced surveillance systems for human and animal diseases would provide early information about new pathogenic microbes. Early warning provides potentially actionable information that can be used to design containment measures and diagnostic tests and to develop new therapies and vaccines. Promote research into nonhuman host-microbe interactions. New pathogenic microbes may use virulence strategies that are fundamentally different from those of known infectious diseases. For example, when HIV burst onto the scene in the 1980s, medical science had no experience with a virus whose pathogenic strategy crippled the immune system and left the host vulnerable to a variety of other lethal infectious diseases. Microbes that are currently pathogenic in plants and invertebrates may pose fundamentally different virulence strategies if they adapt to the human host. Today, medical research needs to be justified concerning its value for human health, and there is often little enthusiasm in diverting scarce research funds into nonhuman diseases. However, it is worth remembering that pioneering work into nonhuman retroviruses in the decades before the HIV epidemic created the knowledge base that allowed rapid progress in developing antiretroviral therapies once HIV was identified as a retrovirus. Promote continued development of antimicrobial therapeutics. The majority of existing antimicrobial therapeutics target microorganisms associated with humans and livestock. However, these represent an infinitesimally small proportion of the microbial life in the biosphere, and there is no guarantee that currently available antimicrobial therapies would be effective against new pathogenic microbes. This is illustrated with C. auris, which is resistant to several of our most effective antifungal agents. Perhaps the greatest insurance against new organisms would be to develop host-targeted therapies that nonspecifically enhance the ability of hosts to resist infectious diseases. Develop threat matrices to identify new likely potential threats. Threat matrices are already used to identify the most worrisome pathogenic microbes for biological warfare and bioterrorism (10), which guide research priorities and expenditures on preparedness measures, such as vaccines. Currently, there is probably not enough information available to construct such threat matrices, but any such exercise would inform on the research needed to obtain the required information. With enhanced information into the types of microbial diseases that affect plants and animals and the temperature tolerance of environmental microbes, it should be possible to develop threat matrices that stratify risk of new infectious diseases.