Microbial conversion of syngas to energy-dense biofuels and valuable chemicals is a potential technology for the efficient utilization of fossils (e.g., coal) and renewable resources (e.g., lignocellulosic biomass) in an environmentally friendly manner. However, gas-liquid mass transfer and kinetic limitations are still major constraints that limit the widespread adoption and successful commercialization of the technology. This review paper provides rationales for syngas bioconversion and summarizes the reaction limited conditions along with the possible strategies to overcome these challenges. Mass transfer and economic performances of various reactor configurations are compared, and an ideal case for optimum bioreactor operation is presented. Overall, the challenges with the bioprocessing steps are highlighted, and potential solutions are suggested. Future research directions are provided and a conceptual design for a membrane-based syngas biorefinery is proposed. (C) 2014 Elsevier Ltd. All rights reserved.