Food contamination with heat‐resistant fungi (HRF), and their spores, is a major issue among fruit processors, being frequently found in fruit juices and concentrates, among other products, leading to considerable economic losses and food safety issues. Several strategies were developed to minimize the contamination with HRF, with improvements from harvesting to the final product, including sanitizers and new processing techniques. Considering consumers’ demands for minimally processed, fresh‐like food products, nonthermal food‐processing technologies, such as high‐pressure processing (HPP), among others, are emerging as alternatives to the conventional thermal processing techniques. As no heat is applied to foods, vitamins, proteins, aromas, and taste are better kept when compared to thermal processes. Nevertheless, HPP is only able to destroy pathogenic and spoilage vegetative microorganisms to levels of pertinence for food safety, while bacterial spores remain. Regarding HRF spores (both ascospores and conidiospores), these seem to be more pressure‐sensible than bacterial spores, despite a few cases, such as the ascospores of Byssochlamys spp., Neosartorya spp., and Talaromyces spp. that are resistant to high pressures and high temperatures, requiring the combination of both variables to be inactivated. This review aims to cover the literature available concerning the effects of HPP at room‐like temperatures, and its combination with high temperatures, and high‐pressure cycling, to inactivate fungi spores, including the main factors affecting spores’ resistance to high‐pressure, such as pH, water activity, nutritional composition of the food matrix and ascospore age, as well as the changes in the spore ultrastructure, and the parameters to consider regarding their inactivation by HPP.