Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue–device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems.