Intense exercise in extreme heat can increase the risk of developing exertional heat stroke (EHS). EHS is 100% survivable with appropriate care, and it is imperative that health care professionals recognize predisposing factors that may increase susceptibility to EHS. Understanding risk factors for EHS will enable clinicians to create effective prevention strategies to improve exercise heat tolerance and mitigate EHS risk. This review addresses new perspectives on risk factors for EHS that focus on hydration, heat acclimatization, medical conditions, climate change and policies, medications, and strength and conditioning sessions.