This perspective originated from our initial environmental assessment of biologics manufacturing as an extension of earlier work on small-molecule pharmaceutics spearheaded by the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR). Systematic analysis was focused on therapeutic proteins due to their current predominance in biotherapeutics. The E factor for process water was found to represent an important environmental index primarily because aqueous solutions are used in practically every processing step, and significant process improvements typically result in sizable reduction in the usage of water and associated chemicals. Compared to small-molecule drugs, manufacture of therapeutic proteins by fermentation requires approximately 10 to 100 times more water per kg of product, but very small amounts of solvent, especially hazardous ones. The amounts of solid waste generated from consumables are comparable between the two groups. A great deal of water is also consumed for non-process operations at bioprocessing plants, which necessitates an E factor for non-process water to help monitor this part of plant operation. Useful environmental indices for biologics manufacturing should also include energy consumption, reportedly dominated by facility operations, especially for cleanroom or controlled space because of the required HVAC (Heating, Ventilation, and Air Conditioning) for its operation. Notable emerging developments for therapeutic protein production include biogenerics, novel bioprocessing technologies, process analytical technology (PAT), single-use (disposable) manufacturing, and alternative production platforms such as cell-free synthesis and transgenic plants or animals. The potential impact of these technologies from an environmental standpoint is discussed.