Background: The past decadeu2019s increased demand for all-ceramic restorations in both anterior and posterior teeth has expanded the search formaterials with improved mechanical and esthetic properties. This evolution in ceramic materials is directly related to the replacementof conventional fabrication processes by computer-aided design/computer-assisted manufacture (CAD/CAM) technology.Aim/Hypothesis: This systematic review sought to determine the long-term clinical survival rates of single-tooth restorations fabricated with CAD/CAMtechnology, as well as the frequency of failures depending on the CAD/CAM system, the type of restoration, the selected material andthe luting agent.Materials and Methods: An electronic search until November 2015 was performed using two databases: Medline/PubMed and Embase. Selected keywordsand well-defined inclusion and exclusion criteria guided the search. All articles were first reviewed by title, then by abstract, andsubsequently by a full text reading. Data were assessed and extracted through a standardized form. The pooled results werestatistically analyzed and the overall failure rate was calculated by random-effects model. In addition, reported failures were analyzedby CAD/CAM system, type of restoration, restorative material, and luting agent.Results: From a total of 2,628 single-tooth restorations with a mean exposure time of 7.3 years and 274 failures, the failure rate was 1.86% peryear, estimated per 100 restoration years (CI 95%: 1.08% to 3.19%). The estimated total survival rate after 5 years was 91.1% (CI95%: 89.6% to 92.5%). Additional findings include the following: (1) The KaVo ARCTICA system had a higher failure rate whencompared to Cerec 2 system (p<0.001; 1.18% vesus 3.22%); (2) Glass-matrix ceramic restorations showed a lower failure rate whencompared to polycrystalline ceramic restorations (p<0.001; 1.18% versus 3.22%); (3) Full-coverage crowns (p<0.001; 1.99%) andendocrowns (p<0.001; 2.57%) showed a higher failure rate when compared to inlay/onlay restorations (1.57%); (4) Chemically curedrestorations (p<0.001; 2.80%) showed a higher failure rate when compared to dual-cured restorations (1.75%) while light-curedrestorations (p<0.001; 1.40%) showed a lower failure.Conclusions and Clinical implications: The overall survival rate of single-tooth ceramic restorations fabricated with CAD/CAM technology was similar to those conventionallymanufactured.