Owing to an increased demand for safe and esthetically pleasing dental materials, ceramics have been developed and optimized to rehabilitate anterior and posterior teeth. This evolution in ceramic materials is directly related to the development of sophisticated processing technologies and systems for use in dental medicine, particularly computer-aided design/computer-assisted manufacture (CAD/CAM) technology. This study is a systematic review outlining long-term clinical survival rates of single-tooth restorations fabricated with CAD/CAM technology with a minimum follow-up of 3 years. A bibliographic search up to September 2016 was performed using two databases: MEDLINE (PubMed) and Embase. Selected keywords and well-defined inclusion and exclusion criteria guided the search of relevant results. All articles were first reviewed by title, then by abstract, and subsequently by a full text reading. Data were assessed and extracted through a standardized form. The pooled results were statistically analyzed, and the overall failure rate was calculated by random effects model. Reported failures were analyzed by CAD/CAM system, type of restoration, restorative material, and luting agent. From a total of 2,916 single-tooth restorations with a mean exposure time of 7.0 years and 351 failures, the failure rate was 2.17% per year, estimated per 100 restoration years (95% confidence interval [CI]: 1.35% to 3.51%). The estimated total survival rate after 5 years was 89.7% (95% CI: 88.1% to 91.1%). The overall survival rate of single-tooth ceramic restorations fabricated with CAD/CAM technology was similar to those conventionally manufactured.