Antimicrobial drug resistance is threatening to take us to the “pre‐antibiotic era”, where people are dying from preventable and treatable diseases and the risk of hospital‐associated infections compromises the success of surgery and cancer treatments. Development of new antibiotics is slow, and alternative approaches to control infections have emerged based on insights into metabolic pathways in host–microbe interactions. Central carbon metabolism of immune cells is pivotal in mounting an effective response to invading pathogens, not only to meet energy requirements, but to directly activate antimicrobial responses. Microbes are not passive players here—they remodel their metabolism to survive and grow in host environments. Sometimes, microbes might even benefit from the metabolic reprogramming of immune cells, and pathogens such as Candida albicans, Salmonella Typhimurium and Staphylococcus aureus can compete with activated host cells for sugars that are needed for essential metabolic pathways linked to inflammatory processes. Here, we discuss how metabolic interactions between innate immune cells and microbes determine their survival during infection, and ways in which metabolism could be manipulated as a therapeutic strategy.