Simultaneous recording of electrophysiology and functional magnetic resonance imaging (fMRI) is a technique of growing importance in neuroscience. Rapidly evolving clinical and scientific requirements have created a need for hardware and software that can be customized for specific applications. Hardware may require customization to enable a variety of recording types (e.g., electroencephalogram, local field potentials, or multi-unit activity) while meeting the stringent and costly requirements of MRI safety and compatibility. Real-time signal processing tools are an enabling technology for studies of learning, attention, sleep, epilepsy, neurofeedback, and neuropharmacology, yet real-time signal processing tools are difficult to develop. We describe an open-source system for simultaneous electrophysiology and fMRI featuring low-noise (<0.6 μV p–p input noise), electromagnetic compatibility for MRI (tested up to 7 T), and user-programmable real-time signal processing. The hardware distribution provides the complete specifications required to build an MRI-compatible electrophysiological data acquisition system, including circuit schematics, print circuit board (PCB) layouts, Gerber files for PCB fabrication and robotic assembly, a bill of materials with part numbers, data sheets, and vendor information, and test procedures. The software facilitates rapid implementation of real-time signal processing algorithms. This system has been used in human EEG/fMRI studies at 3 and 7 T examining the auditory system, visual system, sleep physiology, and anesthesia, as well as in intracranial electrophysiological studies of the non-human primate visual system during 3 T fMRI, and in human hyperbaric physiology studies at depths of up to 300 feet below sea level.