In order to reduce greenhouse gas emissions, cooling technologies based on natural refrigerants with negligible or insignificant effect on the environment and climate have experienced a renaissance in recent years. A variety of highly efficient applications has been developed and has now reached a technical level that makes their use economically viable. Nevertheless, natural refrigerants require careful handling. This guidance document provides a legislative overview for natural refrigerants, technical guidelines, as well as selected practical recommendations. It focusses on safety concerns originating from flammability, toxicity or high working pressures.