This paper aimed to provide a literature review of the mechanical and biological properties of zirconia-reinforced lithium silicate glass-ceramics (ZLS) in Computer-aided design / Computer-aided manufacturing (CAD/CAM) systems. An extensive search of the literature for papers related to ZLS was made on the databases of PubMed/Medline, Scopus, Embase, Google Scholar, Dynamed, and Open Grey. The papers were selected by 3 independent calibrated reviewers. The search strategy produced 937 records. After the removal of duplicates and the exclusion of papers that did not meet the inclusion criteria, 71 papers were included. After reviewing the included records, it was found that two types of ZLS (Vita Suprinity PC; Vita Zahnfabrik and Celtra Duo; Dentsply Sirona) are nowadays available on the market for CAD/CAM systems, similar in their chemical composition, microstructure, and biological-mechanical properties. ZLS is reported to be a biocompatible material, whose fracture resistance can withstand physiological chewing loads. The firing process influences the improvements of strength and fatigue failure load, with a volumetric shrinkage. To date, ZLS can be considered a viable alternative to other glass-ceramics for fixed single restorations. . As to biocompatibility and mechanical properties of ZLS, data are still scarce, often controversial and limited to short-term observational periods. These promising ceramics require further in vitro/in vivo studies to accurately define mechanical and biological properties, mainly in the long-term performance of restorations produced with such materials.