Non-O157 Shiga toxin-producing Escherichia coli (non-O157 STEC) strains have emerged as important foodborne pathogens worldwide. Non-O157 STEC serogroups O26, O45, O103, O111, O121, and O145 have been declared as adulterants in beef by the U. S. Department of Agriculture Food Safety and Inspection Service. While documentation is limited, treatments including heat and acid that have been shown to inactivate E. coli O157:H7 will likely also destroy non-O157 STEC; however, non-O157 STEC strains show variability in their responses to stress. It has been shown that non-O157 STEC may survive in fermented sausages and cheeses, and treatments such as high pressure may be necessary to eliminate non-O157 STEC from these products. The mechanisms used by non-O157 STEC to resist acid environments are similar to those used by O157:H7 strains and include the acid tolerance response, the oxidative system, and the glutamate and arginine decarboxylase systems. However, one study demonstrated that some non-O157 STEC strains utilize a chaperone-based acid stress response (HdeA and HdeB) to combat acidic conditions, which is lacking in E. coli O157:H7. Genomic studies suggest that while non-O157 STEC can cause diseases similar to those caused by E. coli O157:H7, O157 and non-O157 STECs have different evolutionary histories. Non-O157 STECs are a heterogeneous group of organisms, and there is currently a limited amount of information on their virulence, fitness, and stress responses, rendering it difficult to draw firm conclusions on their behavior when exposed to stress in the environment, in food, and during processing.