The availability of refrigerants having low global warming potential (GWP) varies between different applications as it is demonstrated by four system types. Unitary air conditioning (high-pressure application) presents a particularly difficult challenge; no single ideal refrigerant exists, and a tradeoff between flammability and GWP seems to be necessary. The probability of finding better-performing, non-flammable, low-GWP fluids is minimal. This viewpoint is based on the findings from a NIST study, which screened a database of 60 million molecules. The search for suitable refrigerants relied on screening this database using filters of environmental acceptance, chemical stability in the system, low toxicity, coefficient of performance (COP and volumetric capacity (Qvol). Thermodynamic performance limits and the fundamental trade-off between the coefficient of performance (COP) and volumetric capacity are also discussed. The performance limits depend on the operating conditions and the cycle design. These limits are represented by Pareto fronts developed for the objective functions COP and volumetric capacity. As expected, the performance of current refrigerants falls below the Pareto front limits.