Hydrofluorocarbons (HFCs) are manufactured for use as substitutes for ozone-depleting substances that are being phased out globally under Montreal Protocol regulations. While HFCs do not deplete ozone, many are potent greenhouse gases that contribute to climate change. Here, new global scenarios show that baseline emissions of HFCs could reach 4.0–5.3 GtCO2-eq yr−1 in 2050. The new baseline (or business-as-usual) scenarios are formulated for 10 HFC compounds, 11 geographic regions, and 13 use categories. The scenarios rely on detailed data reported by countries to the United Nations; projections of gross domestic product and population; and recent observations of HFC atmospheric abundances. In the baseline scenarios, by 2050 China (31%), India and the rest of Asia (23%), the Middle East and northern Africa (11%), and the USA (10%) are the principal source regions for global HFC emissions; and refrigeration (40–58%) and stationary air conditioning (21–40%) are the major use sectors. The corresponding radiative forcing could reach 0.22–0.25 W m−2 in 2050, which would be 12–24% of the increase from business-as-usual CO2 emissions from 2015 to 2050. National regulations to limit HFC use have already been adopted in the European Union, Japan and USA, and proposals have been submitted to amend the Montreal Protocol to substantially reduce growth in HFC use. Calculated baseline emissions are reduced by 90% in 2050 by implementing the North America Montreal Protocol amendment proposal. Global adoption of technologies required to meet national regulations would be sufficient to reduce 2050 baseline HFC consumption by more than 50% of that achieved with the North America proposal for most developed and developing countries.