The term ecophysiology suggests that a natural connection exists between microbial ecology and microbial physiology, the former being concerned with the responses of microbial populations to environmental influences, and the latter with activities within individual cells. In this contribution we choose to integrate these as far as possible and also indicate how understanding of both is benefiting from advances in molecular biology and informatics. We consider how microbial dispersal relates to microbial survival, recovery and proliferation, including the significance of random factors (stochasticity) in continuation of bacterial lineages, observing that minor environmental changes, can greatly influence the potential for food-borne disease. Homeostasis and membrane transport are identified as potential targets to control food-borne pathogens and the role of compatible solutes in stress protection is presented. Phenotypic variation in genetically homogeneous populations is highlighted as a major component of the overall microbial survival strategy. The marked influence and potential of predictive microbiology as an aid to food safety management is discussed, as is the need for greater knowledge of the ecophysiology of microbes in the growth/no growth region. The application of fundamental scientific principles, including thermodynamics, chemistry and microbial physiology is advocated as the basis for development of theory underpinning microbial ecophysiology. Advancing microbial food safety continues to require development of rapid, quantitative methods as an early warning system and mechanism to curtail microbial food-borne disease outbreaks. However, advances made by technologists and molecular biologists must be combined with knowledge of ecophysiology: e.g. biological rates will continue to constrain resolution of the recalcitrant problem of reducing the time required for enrichment processes. The discussion presented leads to the conclusion that microbial and molecular methods are appropriate for enumeration and prevalence studies but that predictive model development should continue for the purposes of comparative process control and to support the risk assessment paradigm. We conclude also that contributions of human error or complacency to microbial food-borne illness will continue to thwart the best efforts of microbiologists and technologists to reduce its incidence. Decision-support technologies reporting in real-time appear to have potential to make objective food safety decisions thereby reducing the impact of human indifference to the application of simple, but effective, food hygiene rules.