The clinical proteomics field has seen enormous growth in the past 20 years, with over 40000 scientific manuscripts published. At the same time, actual clinical application of the reported findings is obviously scarce. In this manuscript we discuss the key issues that may be responsible for this apparent lack of success, which cannot be measured by the numbers of publications, but by the impact on patient management and treatment. We proceed with suggestions for potential solutions, which include keeping a strict focus on potential patient benefit. We hope this manuscript can help shaping the field, so it can in fact deliver on its realistic promise, to bring significant improvement in management and care to patients.