Closed-loop electrophysiology systems have two main parts, viewed from the animal's perspective: an output (efferent) side, which acquires data from the neural system, and a sensory (afferent) side, which influences the neural system. Among the many ways to acquire neural signals (including electroencephalography, functional magnetic resonance imaging, magnetoencephalography, optical imaging, etc.), we focus on extracellular multi-microelectrode array (MEA) recordings. Likewise, there are many possible ways to alter neural activity: via the animal's own sensory system, with electrical stimulation, pharmacology, optical control of ion channels (Zhang et al., 2007), etc. We focus on delivering neural stimuli via MEAs. Although MEAs are a proven mode of acquiring neural data for a range of prostheses and preparations (Chapin and Moxon, 2000; Taketani and Baudry, 2006), they are less often used for delivering stimulation patterns, with the notable and very successful exception of cochlear prostheses. Motor prostheses, such as artificial limbs, would benefit from having artificial sensory feedback (tactile, kinesthetic). Sensory prostheses and brain stimulation therapies might adapt to the users’ needs more quickly or effectively if they recorded and rapidly responded to the effects of their neural stimuli. Therapeutic and research tools enabled with closed-loop technology can deliver complex stimulation via many microelectrodes, while neural responses are continuously monitored via the same set of microelectrodes to influence subsequent stimulation. Integrated, responsive hybrid neural systems, comprised of both living and artificial components, will someday be commonplace.