The quest to decipher protein alterations in cancer has spanned well over half a century. The vast dynamic range of protein abundance coupled with a plethora of isoforms and disease heterogeneity have been formidable challenges. Progress in cancer proteomics has substantially paralleled technological developments. Advances in analytical techniques and the implementation of strategies to de-complex the proteome into manageable components have allowed proteins across a wide dynamic range to be explored. The massive amounts of data that can currently be collected through proteomics allow the near-complete definition of cancer subproteomes, which reveals the alterations in signalling and developmental pathways. This allows the discovery of predictive biomarkers and the annotation of the cancer genome based on proteomic findings. There remains a considerable need for infrastructure development and the organized collaborative efforts to efficiently mine the cancer proteome.