The mass gathering of people is a potential source for developing, propagating, and disseminating infectious diseases on a global scale. Of the illnesses associated with mass gatherings, respiratory tract infections are the most common, the most easily transmitted, and the most likely to be spread widely beyond the site of the meeting by attendees returning home. Many factors contribute to the spread of these infections during mass gatherings, including crowding, the health of the attendees, and the type and location of meetings. The annual Hajj in the Kingdom of Saudi Arabia is the largest recurring single mass gathering in the world. Every year more than 10 million pilgrims attend the annual Hajj and Umrah. Attendees assemble in confined areas for several days. People with a wide range of age, health, susceptibility to illness, and hygiene sophistication come in close contact, creating an enormous public health challenge. Controlling respiratory infections at the Hajj requires surveillance, rapid diagnostic testing, and containment strategies. Although the Hajj is without equal, other mass gatherings can generate similar hazards. The geographic colocalization of the Zika virus epidemic and the 2016 Summer Olympic Games in Brazil is a current example of great concern. The potential of international mass gatherings for local and global calamity calls for greater global attention and research.