Mass gatherings create challenges to timely medical response. These challenges become amplified when medically and sociologically vulnerable individuals attend. Such at-risk persons may include, but certainly are not limited to, pregnant women, children, the elderly, people with chronic medical conditions, and those with one or more forms of disabilities. When planning for mass gatherings, or when directly managing large assemblies of persons that have evolved subsequent to mass evacuations of displaced persons retreating from a disaster, military conflict, or other humanitarian crisis, experience has shown that prospective preparedness and contingency planning addressing the needs of the entire community, including at-risk populations, facilitates better outcomes for all. Depending on the specific mass gathering, there will always be a variation in the unique concerns, event-driven nuances and potential at-risk populations in attendance for each. However, one recommended generic strategy to help provide a more unified and methodical approach to planning for at-risk persons is the Communication, Maintaining Health, Independence, Support and Safety and Transportation (CMIST) Framework. The CMIST framework has been shown to an extremely useful tool that can help event organizers and emergency managers better anticipate the various needs of these at-risk populations under a variety of mass gathering scenarios worldwide.