Environmental concerns have created need to find replacements for HFC and in some cases HCFC refrigerants used in screw compressor applications. Like most refrigerant changes it becomes necessary to assess the best lubricant option in order to maintain system reliability and performance. Regardless of the magnitude of the changes it allows opportunity to appraise alternative lubricant chemistries that are different from what was used in the past.This paper will investigate various alternative refrigerants being evaluated for screw compressor applications. Choices will be presented that not only maintain what was seen in the past but also offers potential to advance application ranges while using of a single lubricant with various operational designs. As always needed when evaluating lubricants and refrigerants, information on the interaction properties along with stability and material compatibility will be presented. Comparisons will be made to legacy data operation and potential improvements will be presented that are available when using combinations of alternative refrigerants and lubricants.