Cognitive behavioral therapy (CBT) is a recommended treatment for depression in people with epilepsy (PWE); however, a recent Cochrane review found that there was insufficient evidence that any psychological therapy is effective. This conclusion provides little help to clinicians who provide interventions for depressed PWE. The aim of this review was to systematically and qualitatively review the literature on the efficacy of CBT for depression in PWE based on randomized controlled trials (RCTs) and case series. We aim to determine patterns in the literature to inform the type of CBT, if any, that should be offered to PWE who are depressed. Databases MEDLINE, PsycINFO, and the Cochrane EBM Reviews were searched via OVID. Selection criteria included the following: (1) participants with epilepsy; (2) use of CBT; (3) valid depression outcome measure; and (4) published in peer-reviewed journal in English. Inclusions of studies were assessed by two independent researchers. We identified 14 outcome papers for 13 CBT trials including 6 randomized controlled trials (RCTs) and 7 case series. Positive effects of CBT on depression were reported in three of six RCTs. A review of their content revealed that all effective RCTs specifically tailored CBT to improve depression. Conversely, two of three RCTs that failed to find depression-related effects focused on improving seizure-control. This pattern was also observed in the case series. Although limited in number and having methodologic limitations, the treatment studies included in our review suggest that interventions tailored toward improving depression are possibly efficacious, whereas those that focus on improving seizure control do not appear to be. However, this review highlights that there is need for further RCTs in this area in order to confirm the possible efficacy of CBT for depression in PWE.