Flammable refrigerants are becoming more widely used in industrial, commercial (stationary and mobile), and residential applications as alternatives to conventional hydrofluorocarbon refrigerants. In addition to having low global warming potential and ozone depletion levels, HVAC&R systems utilizing these alternative refrigerants have demonstrated improved performance and energy efficiencies. However, despite these advantages, flammable refrigerants pose an increased fire risk over conventional non-flammable refrigerants in the end-use. In this paper, the thermodynamic cycle pressures, temperatures, and efficiencies of several common flammable and non-flammable refrigerants are compared. Typical hazard scenarios for light commercial and residential applications are illustrated with event trees, hazard thresholds are discussed, and some precautions are given. Lessons learned through case studies and conducted research projects are also presented and concluded with recommendations when working with flammable refrigerants.