Colorectal cancer (CRC) is the third most common cancer worldwide. Successful treatment is heavily dependent on tumor stage at the time of detection, but unfortunately CRC is often only detected in advanced stages. New biomarkers in the form of genes or proteins that can be used for diagnosis, prognostication, follow-up, and treatment selection and monitoring could be of great benefit for the management of CRC. Furthermore, proteins could prove valuable new targets for therapy. Therefore, clinical proteomics has gained a lot of scientific interest in this regard. To get an overall insight into the extent to which this research has contributed to a better management of CRC, we give a comprehensive overview of the results of proteomics research on CRC, focusing on expression proteomics, in other words, protein profiling studies. Furthermore, we evaluate the potential of the discriminating proteins identified in this research for clinical use as biomarkers for (early) diagnosis, prognosis and follow-up of CRC or as targets for new therapeutic regimens.