Mussels Mytilus galloprovincialis have been used as model bivalves to study the impacts of global warming on their physiological performance in Themaikos Gulf, North Greece. The studies have been conducted under laboratory and field conditions for more than 6 years and focused on the biochemical, metabolic, physiological and energetic responses of M. galloprovincialis to increases in the ambient temperature. Here we summarize the findings concerning the responses of mussels to environmental temperature, present an integrated model of their physiological performance during thermal stress and discuss these findings in the light of the predicted temperature changes in the Thermaikos Gulf from the regional climate trends and the mean global temperature projections for the period 1990–2100 based on IS92 emission scenarios of the Intergovernmental Panel for Climate Change (IPCC). Our findings indicate that mussels in Themaikos Gulf currently face the temperatures close to their upper thermal limits, especially during the summer, and thus are likely vulnerably to any further increase in the temperature such as expected during the global warming