The concept of Process Analytical Technology (PAT) introduced by the US FDA has received a lot of attention lately. The use of such a scheme ensures robust process performance over the entire life cycle of the product and consistent product quality at the end of the manufacturing process. Successful implementation of PAT requires use of high resolution, orthogonal analytical tools that are able to measure the critical quality attributes (CQA) of the raw materials and in-process materials with the aim of ensuring final product quality. This article presents a review of PAT applications for monitoring commonly used downstream biotech unit operations. Focus of the review will be on recent advancements (last 5 years). Analytical tools that have been used in these approaches have also been discussed with reference to their speed of analysis, robustness and sensitivity. Also discussed is their potential to replace the traditional high performance liquid chromatography (HPLC) which continues to be the gold standard for analysis of biotech therapeutics. (c) 2014 Society of Chemical Industry