Two-phase partitioning bioreactors (TPPBs) allow the biological removal of volatile organic compounds (VOCs) from contaminated gas streams at unprecedented rates and concentrations. TPPBs are constructed by adding a non-aqueous phase (e.g. hexadecane, silicone oil) to an aqueous phase that contains the microorganisms responsible for degrading the VOCs. Presence of a water-immiscible phase improves the transfer of hydrophobic substrates (e.g. hexane, oxygen) or reduces the toxicity of inhibitory substances (e.g. benzene, toluene) to the microorganisms present in the aqueous phase. The non-aqueous phase is selected based on cost, safety, good partitioning properties towards the target pollutants, biocompatibility, and non-biodegradability. TPPBs have hitherto been designed as laboratory-scale well-mixed stirred-tank reactors or as biofilters that contain a non-aqueous phase. Scale-up and industrial use of TPPBs require elucidation and modeling of the mechanisms of substrate transfer and uptake; understanding of the mechanisms of microbial selection; identification or synthesis of new inexpensive and robust non-aqueous phases; and generation of suitable guidelines for process design and control.