With the recent developments in proteomic technologies, a complete human proteome project (HPP) appears feasible for the first time. However, there is still debate as to how it should be designed and what it should encompass. In ‘‘proteomics speak'', the debate revolves around the central question as to whether a gene-centric or a protein-centric proteomics approach is the most appropriate way forward. In this paper, we try to shed light on what these definitions mean, how large-scale proteomics such as a HPP can insert into the larger omics chorus, and what we can reasonably expect from a HPP in the way it has been proposed so far.