Our increased interest in translational research has created a large demand for blood, tissue, and other clinical samples, which find use in a broad variety of research including genomics, proteomics, and metabolomics. Hundreds of millions of dollars have been invested internationally on the collection, storage, and distribution of samples. Nevertheless, many researchers complain in frustration about their inability to obtain relevant and/or useful samples for their research. Lack of access to samples, poor condition of samples, and unavailability of appropriate control samples have slowed our progress in the study of diseases and biomarkers. In this perspective, I focus on five major challenges that thwart clinical sample use for translational research and propose near term objectives to address them. They include: (1) defining our biobanking needs; (2) increasing the use of and access to standard operating procedures; (3) mapping interobserver differences for use in normalizing diagnoses; (4) identifying natural internal protein controls; and (5) redefining the clinical sample paradigm by building partnerships with the public. In each case, I believe that we have the tools at hand required to achieve the objective within 5 years. Potential paths to achieve these objectives are explored. However we solve these problems, the future of proteomics depends on access to high quality clinical samples, collected under standardized conditions, accurately annotated and shared under conditions that promote the research we need to do.