This Perspective discusses the literature related to two-phase biocatalysis in microfluidic droplets. Enzymes used as catalysts in biocatalysis are generally less stable in organic media than in their native aqueous environments; however, chemical and pharmaceutical compounds are often insoluble in water. The use of aqueous/organic two-phase media provides a solution to this problem and has therefore become standard practice for multiple biotransformations. In batch, two-phase biocatalysis is limited by mass transport, a limitation that can be overcome with the use of microfluidic systems. Although, two-phase biocatalysis in laminar flow systems has been extensively studied, microfluidic droplets have been primarily used for enzyme screening. In this Perspective, we summarize the limited published work on two-phase biocatalysis in microfluidic droplets and discuss the limitations, challenges, and future perspectives of this technology.