Purpose: The introduction of computer-aided design/computer-assisted manufacture (CAD/ CAM) technology into removable denture prosthodontics enables denture adaptation in fewer patient visits, an advantage that appeals to dentists and patients. Since manufacturers follow very different approaches, an evaluation of the different clinical CAD/CAM complete denture fabrication protocols is desirable. The aim of this article is to assess and evaluate the different clinical fabrication protocols of currently available CAD/CAM denture systems to provide decision support for dental practitioners. Materials and Methods: The information for the present article was gathered by questionnaires from (in alphabetical order) Global Dental Science, Merz Dental, Wieland Dental + Technik, Ivoclar Vivadent, VITA Zahnfabrik, and Whole You, and complemented with results from the authors' clinical experience. Results: Wieland Digital Denture involves four patient visits. Both AvaDent digital dentures and Whole You Nexteeth enable denture fabrication in three (including a try-in session) or two (without try-in) visits. Baltic Denture System stipulates complete denture fabrication in two visits, and VITA VIONIC material system is an open system enabling choice between different treatment protocols. It can be combined with several open scanners, CAD software options, and milling machines. Conclusion: The available CAD/CAM denture fabrication systems provide a variety of advantages, and the decision on a system should depend on the dentist's prosthodontic expertise, patient throughput rate, and requirements regarding denture individualization.