This review focuses on the responses of microbial spores to food processes that incorporate high hydrostatic pressures. While the majority of information deals with spores of Bacillus species, spores of Clostridium and Alicyclobacillus species are also discussed, and a section of the review surveys the responses of fungal spores to high-pressure processing. The mechanisms of the germination of bacterial spores are outlined in detail with regard to spore physiology and structure, along with molecular aspects of germinants and the interaction with spore receptors. Use of treatments combining pressure and temperature for a range of different food products is reviewed, including examples of hurdle technology employing high hydrostatic pressure. Pressure-assisted thermal sterilization is also discussed.