Hydrofluorocarbons (HFCs) and so-called hydrofluoroolefins (HFOs) are used as refrigerants in air conditioning, refrigeration, chillers, heat pumps and devices for dehumidification and drying. However, many HFCs, including R-134a and R-125, have a high global warming potential and some of the HFCs and HFOs degrade atmospherically and form trifluoroacetic acid (TFA) as a persistent degradation product. Rising levels of TFA around the globe reveal an urgent need to replace fluorinated refrigerants with non-fluorinated working fluids to avoid direct emissions due to leakage, incorrect loading or removal. It is important, however, also to select refrigerants with high efficiencies to avoid increasing indirect CO₂ emissions due to higher energy consumption during the use phase. The present study investigates the available non-fluorinated alternatives to fluorinated refrigerants and shows that a transition to non-fluorinated refrigerants, in general, is possible and has happened in many sectors already. Technically, there are only slight barriers to overcome in order to replace fluorinated refrigerants in almost all newly developed systems conforming to existing standards. Additionally, we show that alternatives are available even for some use cases for which derogations have been proposed in the EU PFAS restriction proposal and suggest making these derogations more specific to support a speedy transition to non-fluorinated refrigerants in all sectors.