Neurostimulation provides a new dimension in the treatment of neurologic disorders. For patients with drug-resistant epilepsy, the Responsive Neurostimulation (RNS) System (NeuroPace, Inc.) provides treatment of seizures with a closed-loop device that continuously records brain activity and provides stimulation designed to reduce seizure frequency over time. The presence of a chronic implanted device that can provide an electrographic record of neural activity provides great opportunities for treatment of seizure disorders and neuroscience research. However, our experience with this device indicates that a number of ethical and clinical challenges arise, and these issues may be applicable to neurotechnology developed for other disease states in the future. We present clinical scenarios based on cases from our center that present clinical or ethical dilemmas. The dilemmas revolve around 4 core themes: (1) electroclinical correlation and dissociation; (2) patient concerns about device capabilities; (3) clinician opportunities and burdens; and (4) data ownership and access. Developing a framework for understanding these issues will be critical as closed-loop neuromodulation is applied to a growing range of neuropsychiatric disorders.