The Human Proteome Project (HPP) annually reports on progress made throughout the field in credibly identifying and characterizing the complete human protein parts list and making proteomics an integral part of multi-omics studies in medicine and the life sciences. NeXtProt release 2019-01-11 contains 17,694 PE1 proteins, which represent 89% of all 19,823 neXtProt predicted coding genes (all PE1, 2, 3, 4 proteins), up from 17,470 in release 2018-01. Conversely, the number of neXtProt PE2, 3, 4 proteins, called the “missing proteins” (MPs), has been reduced from 2,949 to 2,129 over the past three years. Since the inception of the Human Proteome Project, PeptideAtlas has been the source of uniformly re-analyzed raw mass spectrometry data for neXtProt. PeptideAtlas gained 495 canonical proteins between 2018 and 2019. Multiple strategies have been employed to detect hard-to-identify proteins. Meanwhile, the Human Protein Atlas has released version 18.1 with immunohistochemical evidence of expression of 17,000 proteins, survival plots as part of the Pathology Atlas, and its Cell Atlas, and is moving toward completion of a harmonized resource on tissue-specific RNA expression data. Many investigators apply multiplexed SRM-targeted proteomics for quantitation of organ-specific popular proteins in studies of various human diseases. The 19 teams of the Biology and Disease-driven B/D-HPP published a total of 382 publications in 2018, bringing proteomics to a broad array of biomedical research.