Downstream processing aims at recovering the target product at the required specifications from the bioreactor effluent. Research and development in this field relies on experimental and mathematical tools at the levels of chemical components, unit operations and processes. Recently, advances have been made in addressing the broth mixture complexity early on, in incorporating high-throughput experimentation for data generation and mechanistic understanding of the separation processes, in improving the materials and scalability of specific unit operations, as well as establishing the potential of process integration concepts. Further developments are expected considering the variety of (non-sugar) feedstocks currently under research, the need to transition to renewable energy sources, and the opportunities for improved scale-up through initiatives as Big Data and digital manufacturing.