After several years of discussion and formal planning, the Human Proteome Organization (HUPO) announced the global Human Proteome Project (HPP) at the Sydney World Congress of Proteomics in September 2010. A year later the Project was launched at the Geneva World Congress.  In 2012 in Boston and in 2013 in Yokohama there was tremendous progress reported by the Chromosome-centric HPP, led by Young-Ki Paik (Korea), Bill Hancock (USA), and Gyorgy Marko-Varga (Sweden), and the Biology and Disease-driven HPP, led by Ruedi Aebersold (Switzerland) and Jennifer van Eyk (USA).  There are now 24 chromosome-centric teams and 16 B/D teams (including the pre-existing HUPO organ and biofluid-based initiatives).  These activities are supported by resource pillars covering the mass spectrometry, protein capture, and knowledge-base domains.  The Journal of Proteome Research in 2013 and in 2014 published special issues with 48 and 32 C-HPP and C-HPP-related articles, respectively.  The HPP stimulated the emergence of ProteomeXchange for submission of all datasets.  PeptideAtlas and GPMDB provide standardized re-analyses of the accumulating data, with appropriate rigorous quality thresholds; Human Protein Atlas provides extensive information on tissue expression by immunohistochemistry; and neXtProt integrates and curates the combined identifications and annotations.  As of the January 2014 Lane et al update (JPR 13:15-20), there were 15,646 confidently identified proteins and 3844 protein-coding genes for which protein-level evidence was missing or insufficient.  Additional large datasets from TCGA, Pandey lab, and Kuster lab, among others, will be subjected to the standardized reanalysis and incorporated into the HPP Metrics.  Many investigators are focused on finding credible evidence for the missing proteins, and many others on characterizing the presence, dynamics, and functions of splice variants, post-translational modifications, and sequence variants.  The B/D-HPP has stimulated development toward robust, moderate-cost, high throughput mass spectrometers (Proteome Analyzer project), and has initiated consensus development of priority protein lists for specific major diseases, like type 2 diabetes and ovarian cancers, for which SRM reagents and spectral libraries are available for use throughout the life sciences and biomedical research community.  Current information about the publications and other activities of the HPP is available at www.thehpp.org and at www.c-hpp.org.  All experimental datasets are expected to be submitted to PRIDE/EBI (MS/MS) or PASSEL/ISB (SRM) to be made available to investigatorsglobally and linked to additional databases and neXtProt through ProteomeXchange.