Major depressive disorder (MDD) is a mental health disorder affecting millions of individuals across the globe. Conventional antidepressants have not proven as effective as initially hoped. Many people are unresponsive to medications and are diagnosed with treatment-resistant depression (TRD). Ketamine, a dissociative anesthetic, has been shown to have a rapid antidepressant effect in individuals with MDD and TRD. However, its neural mechanisms are poorly understood. This systematic review aimed to identify the neural correlates of response to ketamine infusion in MDD and TRD patients. Specifically, our goal was to review functional changes associated with ketamine treatment, as assessed with functional neuroimaging methods. Understanding the neural correlates of ketamine response can help identify biomarkers that predict individual treatment outcomes in patients with TRD. A systematic search in three databases yielded 608 articles, of which 11 were included in this review. Findings demonstrated a rapid onset of action following administration of a small dose of ketamine, which correlated with reductions in depression rating scores. Furthermore, results showed alterations in functional connectivity and metabolism between and within regions implicated in the default mode, central executive, and salience networks. Alterations in activation in areas associated with emotional and reward processing were observed during task-based functional magnetic resonance imaging (fMRI). The convergence of findings across studies suggests a common theme of normalization of activity (indicating a return to a typical activity level seen in healthy individuals) within brain regions involved in depression symptomatology.