A comprehensive overview of the application of proteomics for the assessment of quality and safety in fishery products is presented in this review. For this purpose, two consecutive phases of the proteomics pipeline used in our laboratory (discovery and target-driven stages), are described in detail. The potentiality of this workflow is emphasized using different subjects concerning fish quality and safety. Fish authentication, allergen detection, microorganism contamination and quality changes during storage and processing are the main topics where proteomics is being successful applied. Future directions and new potential perspectives are also provided.