Microbial fuel cells (MFCs) have continued to offer the potential to increase treatment efficiency, power generation, and energy recovery during wastewater treatment, and have garnered considerable research interest over the past 15 years. For the time being, the potential of this technology remains unfulfilled as scaling-up MFC reactors has presented a significant engineering challenge. The recent development of materials and designs that reduce fabrication costs in addition to maintaining high performance at increased reactor sizes has brought MFCs a step closer to practical application. The optimization of operating conditions has led to additional improvements in performance and has further increased the feasibility of these technologies. Herein, the fundamental concepts governing MFC performance are detailed along with highlighting developments in materials, designs, and operating conditions with the hope of promoting future scale-up efforts and a more sustainable wastewater treatment infrastructure.