As a result of climate change, heat waves are expected to increase in severity and frequency. Hot weather extremes appear to have a profound effect on human health and well-being. In addition, humidity affects human comfort, and the perceived temperature by humans is largely dependent on atmospheric moisture content. The danger posed by the combined effect of air temperature and humidity has lead biometeorologists to develop various discomfort indices in order to define the danger and alert the pubic. In this study, the discomfort conditions were estimated by using several biometeorological indices: the discomfort index, relative strain index, heat index and humidex, during the summer period (June, July and August) for the years 1970-2005, based on long-term meteorological data. During the heat waves, the results for the biometeorological discomfort indices (for that time period) indicate a high thermal stress on people in the center of Thessaloniki.