With the availability of its complete genome sequence and unique biological features relevant to human disease,Caenorhabditis eleganshas become an invaluable model organism for the studies of proteomics, leading to the elucidation of nematode gene function. A journey from the genome to proteome ofC. elegansmay begin with preparation of expressed proteins, which enables a large-scale analysis of all possible proteins expressed under specific physiological conditions. Although various techniques have been used for proteomic analysis ofC. elegans, systematic high-throughput analysis is still to come in order to accommodate studies of post-translational modification and quantitative analysis. Given that no integratedC. elegansprotein expression database is available, it is about time that a globalC. elegansproteome project is launched through which datasets of transcriptomes, protein–protein interaction and functional annotation can be integrated. As an initial target of a pilot project of theC. elegansproteome project, the cholesterol-mediated signaling pathway will be an excellent example since, like in other organisms, it is one of the key controlling pathways in cell growth and development inC. elegans. As this field tends to broaden to functional proteomics, there is a high demand to develop the versatile proteome informatics tools that can mange many different data in an integrative manner.