Formation of highly resistant spores is a concern for the safety of low-acid foods as they are a perfect vehicle for food spoilage and/or human infection. For spore inactivation, the strategy usually applied in the food industry is the intensification of traditional preservation methods to sterilization levels, which is often accompanied by decreases of nutritional and sensory properties. In order to overcome these unwanted side effects in food products, novel and emerging sterilization technologies are being developed, such as pressure-assisted thermal sterilization, high-pressure carbon dioxide, high-pressure homogenization, and cold plasma. In this review, the application of these emergent technologies is discussed, in order to understand the effects on bacterial spores and their inactivation and thus ensure food safety of low-acid foods. In general, the application of these novel technologies for inactivating spores is showing promising results. However, it is important to note that each technique has specific features that can be more suitable for a particular type of product. Thus, the most appropriate sterilization method for each product (and target microorganisms) should be assessed and carefully selected.