The field of clinical proteomics has seen enormous growth in the past 20 years, with over 40,000 scientific manuscripts published to date. At the same time, actual clinical application of the reported findings is obviously scarce. In this viewpoint article, we discuss the key issues that may be responsible for this apparent lack of success. We conclude that success must not be assessed based on the number of publications, but via the impact on patient management and treatment. We proceed with specific suggestions for potential solutions, which include keeping a strict focus on potential patient benefit. We hope this article can help shape the field, so it can in fact deliver on its realistic promise to bring significant improvement in management and care to patients.