The eastern Mediterranean and Middle East, a region with diverse socioeconomic and cultural identities, is exposed to strong climatic gradients between its temperate north and arid south. Model projections of the twenty-first century indicate increasing hot weather extremes and decreasing rainfall. We present model results, which suggest that across the Balkan Peninsula and Turkey climate change is particularly rapid, and especially summer temperatures are expected to increase strongly. Temperature rise can be amplified by the depletion of soil moisture, which limits evaporative cooling, prompted by the waning of large-scale weather systems that generate rain. Very hot summers that occurred only rarely in the recent past are projected to become common by the middle and the end of the century. Throughout the region, the annual number of heat wave days may increase drastically. Furthermore, conditions in the region are conducive for photochemical air pollution. Our model projections suggest strongly increasing ozone formation, a confounding health risk factor particularly in urban areas. This adds to the high concentrations of aerosol particles from natural (desert dust) and anthropogenic sources. The heat extremes may have strong impacts, especially in the Middle East where environmental stresses are plentiful.