PURPOSE: To review the current published literature on the use of spectral domain (SD) OCT to help detect changes associated with the diagnosis of glaucoma. METHODS: Searches of the peer-reviewed literature were conducted on June 11, 2014, November 7, 2016, August 8, 2017, and April 19, 2018, in the PubMed and Cochrane Library databases and included only articles published since the last glaucoma imaging Ophthalmic Technology Assessment, which included articles up until February 2006. The abstracts of these 708 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 74 articles were selected, and the panel methodologist (K.N.-M.) assigned ratings to them according to the level of evidence. Two articles were rated level I, 57 articles were rated level II, and the 15 level III articles were excluded. RESULTS: Spectral-domain OCT is capable of detecting damage to the retinal nerve fiber layer (RNFL), macula, and optic nerve in patients with preperimetric and perimetric glaucoma (level I and II evidence). The most commonly studied single parameter was RNFL thickness. Of note, RNFL thickness measurements are not interchangeable between instruments. Various commercially available SD OCT instruments have similar abilities to distinguish patients with known glaucoma from normal subjects. Despite different software protocols, all SD OCT instruments are able to detect the same typical pattern of glaucomatous RNFL loss that affects primarily the inferior, inferior temporal, superior, and superior temporal regions of the optic nerve (level II evidence). Across many SD OCT instruments, macular imaging also can detect a preferential inferior, inferior temporal, and superior temporal thinning in patients with glaucoma compared with controls. Best disc parameters for detecting glaucomatous nerve damage are global rim area, inferior rim area, and vertical cup-to-disc ratio. Studies suggest that newer reference-plane independent optic nerve parameters may have the same or better detection capability when compared with older reference-plane dependent disc parameters (level II evidence). CONCLUSIONS: Structural glaucomatous damage can be detected by SD OCT. Optic nerve, RNFL, and macular parameters can help the clinician distinguish the anatomic changes that are associated with patients with glaucoma when compared with normal subjects.