The advantages of synthetic chemistry performed in continuous flow synergize with the benefits conferred by biocatalysis, including reactions with greener, milder, lower temperatures, and aqueous conditions. Furthermore, the fine control over reaction conditions in continuous flow can solve inherent challenges associated with catalysis by enzymes, such as substrate and product inhibition. Cells and enzymes also benefit from the improved mixing, mass transfer, thermal control, pressurized processing, decreased variation, automation, along with in-line product analysis and purification conferred through continuous flow. Thus, the combination of continuous flow and biocatalysis has emerged as a highly effective approach for creating diverse synthetic targets. Examples include immobilized enzymes and whole cells in continuous flow for the synthesis of pharmaceuticals, chemicals, and materials. Challenges to continuous-flow biocatalysis surveyed in this chapter include immobilization methods, the necessity to regenerate cofactors for cell-free biocatalysis, and optimization of biosynthetic steps with highly divergent conditions in flow.