This paper reviews significant contributions to the evidence for the use of quantitative electroencephalography features as biomarkers of depression treatment and examines the potential of such technology to guide pharmacotherapy. Frequency band abnormalities such as alpha and theta band abnormalities have shown promise as have combinatorial measures such as cordance (a measure combining alpha and theta power) and the Antidepressant Treatment Response Index in predicting medication treatment response. Nevertheless, studies have been hampered by methodological problems and inconsistencies, and these approaches have ultimately failed to elicit any significant interest in actual clinical practice. More recent machine learning approaches such as the Psychiatric Encephalography Evaluation Registry (PEER) technology and other efforts analyze large datasets to develop variables that may best predict response rather than test a priori hypotheses. PEER is a technology that may go beyond predicting response to a particular antidepressant and help to guide pharmacotherapy.