The need for renewable and sustainable fuel and energy storage sources is pressing. Biohydrogen has the potential to be a storable energy carrier, a direct fuel and a diverse building block for various downstream products. Utilizing microbial electrolysis cells (MECs) to produce biohydrogen from residue streams, such as the organic fraction of municipal solid waste (OFMSW), agricultural residues and wastewater facilitate utilization and energy recovery from these streams, paving the path for a circular economy. The advantages of using hydrogen include high gravimetric energy density and, given the MEC pathway, the ability to capture heavy metals, ammonia and phosphates from waste streams, thereby allowing for multiple revenue streams emanating from MECs. A review of the MEC technology and its application was carried out to investigate the use of MEC in sustainable biohydrogen production. This review summarizes different MEC designs of varying scales, including anode materials, cathode materials, and configuration possibilities. This review highlights the accomplishments and challenges of small-scale to large-scale MECs. Suggestions for improving the successful upscaling of MECs are listed, thus emphasizing the areas for continued research.