There is an urgent need for an effective therapy for treatment-refractory mental illness. Trials ongoing globally that explore surgical treatment, such as deep brain stimulation, for refractory psychiatric disease have produced some promising early results. However, diverse inclusion criteria and variable methodological and ethical standards, combined with the sordid past of neuromodulation, confound trial interpretation and threaten the integrity of a new and emerging science. What is required is a standard of ethical practice, globally applied, for neurosurgical trials in psychiatry that protects patients and maintains a high ethical benchmark for clinicians and researchers to meet. With mental illness, as well as treatment resistance, reaching epidemic proportions, ethically and scientifically sound clinical trials will lead to effective and safe surgical treatments that will become vital components of the clinicians' armamentarium. Ethical criteria, such as the ones proposed here, need to be established now and applied in earnest if the field is to move forward and if patients with no other therapeutic options are to receive much-needed treatment.