The advent of environmentally friendly refrigerants and the global drive for higher efficiency is bringing change to our industry. A review of current HFC refrigerants and their lubricant choices over a range of evaporator temperatures will be summarized and compared to the numerous low GWP refrigerant replacements and associated lubricant considerations. The paper details a methodology for matching a refrigerant and a lubricant over a variety of low GWP refrigerant options. The current challenges in meeting miscibility, solubility, discharge temperature and working viscosity targets will be discussed and options presented. As the industry develops and implements both interim, lower GWP alternatives and long-term low or ultra-low GWP refrigerant options, in some cases the door has opened for development of new or optimized lubricant chemistries which are both compatible with the new refrigerants and also maintain or improve equipment performance and reliability. For example, CPI recognizes that the solubility characteristics of the low GWP refrigerants in many cases are different than the incumbent HFC refrigerants. CPI has investigated the solubility characteristics of new refrigerants and has developed innovative lubricant formulations to control solubility to minimize the need for equipment hardware or operating changes. While low GWP refrigerants are environmentally friendly with a shorter atmospheric life, in some cases either the refrigerants or the equipment operating conditions will bring about system chemistry concerns that didn’t exist with the stable HFC refrigerants such as R-134a. CPI will discuss methods to monitor for lubricant and refrigerant stability in a refrigeration system, and options to mitigate chemical stability concerns. The information shared in this presentation will provide a 360-degree view of the important aspects of matching a refrigerant to a lubricant for successful and reliable equipment operation.