Human exposure to a hot environment may result in various heat-related illnesses (HRIs), which range in severity from mild and moderate forms to life-threatening heatstroke. The Hajj is one of the largest annual mass gatherings globally and has historically been associated with HRIs. Hajj attracts over two million Muslim pilgrims from more than 180 countries to the holy city of Makkah, Kingdom of Saudi Arabia. Several modifiable and non-modifiable factors render Hajj pilgrims at increased risk of developing HRIs during Hajj. These include characteristics of the Hajj, its location, population, and rituals, as well as pilgrims' knowledge of HRIs and their attitude and behavior. Makkah is characterized by a hot desert climate and fluctuating levels of relative humidity. Pilgrims are very diverse ethnically and geographically, with different adaptations to heat. Significant proportions of the Hajj population are elderly, obese, and with low levels of fitness. In addition, many have underlying health conditions and are on multiple medications that can interfere with thermoregulation. Other factors are inherent in the Hajj and its activities, including crowding, physically demanding outdoor rituals, and a high frequency of infection and febrile illness. Pilgrims generally lack awareness of HRIs, and their uptake of preventive measures is variable. In addition, many engage in hazardous behaviors that increase their risk of HRIs. These include performing rituals during the peak sunshine hours with no sun protection and with suboptimal sleep, nutrition, and hydration, while neglecting treatment for their chronic conditions. HRIs preventive plans for Hajj should incorporate measures to address the aforementioned factors to reduce the burden of these illnesses in future Hajj seasons. Lessons from the Hajj can be used to inform policy making and HRIs preventive measures in the general population worldwide.