There is growing interest in substituting existing refrigerants with low global warming potential (GWP) refrigerants, including naturally occurring fluids, to reduce the impact of human activities on climate change. In the Part I of the study, we examined 13 refrigerants from the perspective of the characteristic shape of their respective temperature–entropy (T-S) and the logarithm of the pressure versus inverse absolute temperature (log P vs. T 1) phase boundary. In Part 2, we are evaluating prospective low-GWP refrigerants in four distinct heat pump cycles using the First and Second laws of thermodynamics. The essence of the study is to establish the performance of the low-GWP refrigerants when deployed in a heat pump system. Exergy analysis provides a true measure of lost work, or systemic inefficiencies, vividly quantifying areas of improvement and identifying the preferred cycle for a refrigerant. The combined knowledge of the properties of the phase boundary on either side of the critical point, and exergy analysis of prospective cycles is necessary for a better perspective on discriminating among refrigerants as hydrochlorofluorocarbons are phased out and replacement refrigerants must be found.