The remarkable efficacy of deep brain stimulation (DBS) for a range of treatment-resistant disorders is still not matched by a comparable understanding of the underlying neural mechanisms. Some progress has been made using translational research with a range of neuroscientific techniques, and here we review the most promising emerging principles. On balance, DBS appears to work by restoring normal oscillatory activity between a network of key brain regions. Further research using this causal neuromodulatory tool may provide vital insights into fundamental brain function, as well as guide targets for future treatments. In particular, DBS could have an important role in restoring the balance of the brain’s default network and thus repairing the malignant brain states associated with affective disorders, which give rise to serious disabling problems such as anhedonia, the lack of pleasure. At the same time, it is important to proceed with caution and not repeat the errors from the era of psychosurgery.