The chemical stability and materials compatibility of refrigerants with lubricants and system materials is a significant design parameter when considering a new refrigerant for use which affects the long term reliability of HVACR products. The new unsaturated hydrofluorocarbons (HFOs) refrigerant chemistries are designed to be unstable in the atmosphere in days rather than years. This unique chemistry opens the possibility that these HFOs could be unstable in HVACR systems. Historically, refrigerant instability was seen with the chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs) but refrigerant stability greatly increased with the transition to hydrofluorocarbons (HFCs). The stability and material compatibility with construction materials challenges were significantly reduced as the HFCs were more thermally and chemically stable with contaminants and for the most part were less reactive with construction materials. AHRI, ASHRAE and other industry organizations have started to conduct investigations into lubricant compatibility, chemical stability, and materials compatibility with the HFO chemistries and some concerns have been raised around HFO refrigerant stability. This paper will provide a historical overview of refrigerant instability seen with CFCs, HCFCs and HFCs to provide a perspective for any instability seen with new HFO chemistries.