Real‐time release testing (RTRT) is defined as “the ability to evaluate and ensure the quality of in‐process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls” (ICH Q8R2). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small‐molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality—with improved productivity including faster release and potentially decreased costs—all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on‐line and in‐line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT. Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26378/full Sensors (process analytical technology, PAT) and control strategies are reviewed that enable real‐time release testing (RTRT) for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on‐line and in‐line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT.