Background: Mood disorders constitute a high burden for both patients and society. Notwithstanding the large arsenal of available treatment options, a considerable group of patients does not remit on current antidepressant treatment. There is an urgent need to develop alternative treatment strategies. Recently, low-strength transcranial pulsed electromagnetic field (tPEMF) stimulation has been purported as a promising strategy for such treatment-resistant depression (TRD). The mode of action of this new technique is however largely unknown. Methods: We searched PubMed for literature reports on the effects of tPEMF and for information regarding its working mechanism and biological substrate. Results: Most studies more or less connect with the major hypotheses of depression and concern the effects of tPEMF on brain metabolism, neuronal connectivity, brain plasticity, and the immune system. Relatively few-studies paid attention to the possible chronobiologic effects of electromagnetic fields. Limitations: We reviewed the literature of a new and still developing field. Some of the reports involved translational studies, which inevitably limits the reach of the conclusions. Conclusion: Weak magnetic fields influence divergent neurobiological processes. The antidepressant effect of tPEMF may be specifically attributable to its effects on local brain activity and connectivity. (C) 2016 Elsevier Inc. All rights reserved.