Applying proteomics technologies in clinical samples poses substantial challenges in both "bench" technologies and in bioinformatics. Through funding by National Cancer Institute programs, clinical proteomics at Vanderbilt has blossomed into a substantial enterprise. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) evaluated the sources of variability in these experiments and how now turned to the application of these technologies in the context of TCGA-characterized tumor samples. The Early Detection Research Network emphasizes the development of biomarkers that enable the recognition of cancer at early stages and that support medical decision-making. Bioinformatics researchers in DBMI are seeking improved algorithms for information recovery from clinical proteomics samples, for recognition of reliable protein differences in complex backgrounds, for pathway assessment from protein data, and for data integration across systems biology platforms.