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Sparked by the article from Lescuyer and colleagues in a recent issue, we aim here to further encourage interest in and discussion of clinically relevant biomarker research. We express our view on proteomics for biomarker discovery by addressing multiple relevant issues, including the inherent differences between biological fluids (and how these differences affect current analytical approaches) and experimental design to maximize the efficiency of moving from the bench to the bedside. Herein, we also include suggestions for definition of the term “biomarker”, based on the use of a set of universal characterization/validation requirements, and illustrate several recent examples of successful transitions of benchtop proteomic studies work to clinical practice.