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Neural interfaces are engineered devices designed to exchange information with the nervous system. Basic neural interface implants already have important medical roles, but there is far greater potential on the horizon if an array of fundamental biophysical and biomedical challenges can be overcome. The challenges fall in the following categories: selectivity—nerves and motor units must be monitored and addressed uniquely in a noise-ridden environment; stability—optimally, surgically implanted interfaces will interact with specific nerves over a time frame of years; resolution versus invasiveness—a balance must be achieved between the density of the signal and the degree to which delicate physiological structures will tolerate the intrusion of the device; and management of host-interface responses—reducing tissue reactions such as inflammation and scarring, which plague implanted devices today, will be critical in achieving selectivity, stability, and resolution in long-term implants. On the horizon, research is being done on single-cell electronic connections—silicon-neuron hybrid circuits—and alternatives to stimulation by electrical current, including genetic modifications to neuronal tissue that produce neurons activatable by light.