OBJECTIVE: To investigate the existing evidence about whether adherence to the Mediterranean diet may have a role as an effect modifier of active and passive smoking on human health. STUDY DESIGN: Review. METHODS: An overview of emerging evidence and published studies that cover the interaction between the Mediterranean diet and smoking. RESULTS: Both epidemiological and laboratory studies have shown that the Mediterranean diet has a protective effect against biochemical and molecular processes that lead to cancer, cardiovascular disease and respiratory illness. Based on the high daily intake of vitamins and antioxidants, the Mediterranean diet is comprised of a number of compounds that could alter certain outcomes related to smoking. Studies have indicated that certain diseases attributable to smoking, such as lung cancer, asthma and cardiovascular disease, are inversely associated with certain antioxidants and lipids. CONCLUSIONS: The literature indicates that the existence of a partial interaction between adherence to the Mediterranean diet and the health effects of smoking is possible. Further research is needed to lead to a conclusive statement on this hypothesis.