To facilitate the advancement in plasma protein analysis using different technologies, across multiple disease states, and providing a framework to catalog and track the associated results and concepts. The HPPP was initiated in 2002 as a means to overcome major challenges (e.g. sensitivity and analytical depth) in plasma proteomics. The HPPP helped provide a strategy to address the growing number of plasma samples being systematically collected, stored, and accessible through biobanks. The HPPP serves to bring together different contributions to plasma proteomics from the perspective of mass spectrometry and affinity-based assays, and provide a platform to discuss success stories, technological possibilities, viewpoints, and perspectives on how plasma proteomics has and will continue to advance. The team published a review on recent advances in plasma proteomics, providing a set of key aspects that should be considered before embarking on a new plasma proteomics study. The review was published in the 2019 HPP Special Issue (Ignjatovic et al. 2019), and has received new coverage as well. During 2021, the team published a follow-up review, highlighting views and perspectives about technological developments and possible clinical applications that use mass-spectrometry or affinity-based methods. We discuss examples where plasma proteomics contributed valuable insights into SARS-CoV-2 infections, aging, and hemostasis and the opportunities offered by combining proteomics with genetic data.