There are a number of commercially available multi-microelectrode electrophysiology systems, but to our knowledge, none was designed with closed-loop applications in mind. Combining multi-microelectrode stimulation with multi-microelectrode recording, and enabling the recorded signals to trigger stimulus patterns dynamically in real time, is still very much at the experimental stage. We developed the first many-electrode system to close the loop around embodied cultured networks of ∼50,000 mammalian brain cells (Potter, 2001). This was comprised of the real-time all-channel stimulator (RACS) (Wagenaar and Potter, 2004) and our open-source MeaBench software suite (Wagenaar et al., 2005b). This system was designed to work with the MultiChannel Systems data acquisition card (MC-Card) and preamp (MEA60). It is modular, open-source, and has been replicated and used by a number of other labs. We have used it in closed-loop mode to suppress epileptiform activity in neural cultures (Wagenaar et al., 2005a), to electrically train cultures on a navigation task (Bakkum et al., 2008), and even to create art (Bakkum et al., 2007). MeaBench, though very flexible, is not very user-friendly, as experiments are carried out by scripting C++ software modules from the Linux command line.