Protein biomarkers offer major benefits for diagnosis and monitoring of disease processes. Recent advances in protein mass spectrometry make it feasible to use this very sensitive technology to detect and quantify proteins in blood. To explore the potential of blood biomarkers, we conducted a thorough review to evaluate the reliability of data in the literature and to determine the spectrum of proteins reported to exist in blood with a goal of creating a Federated Database of Blood Proteins (FDBP). A unique feature of our approach is the use of a SQL database for all of the peptide data; the power of the SQL database combined with standard informatic algorithms such as BLAST and the statistical analysis system (SAS) allowed the rapid annotation and analysis of the database without the need to create special programs to manage the data. Our mathematical analysis and review shows that in addition to the usual secreted proteins found in blood, there are many reports of intracellular proteins and good agreement on transcription factors, DNA remodelling factors in addition to cellular receptors and their signal transduction enzymes. Overall, we have catalogued about 12,130 proteins identified by at least one unique peptide, and of these 3858 have 3 or more peptide correlations. The FDBP with annotations should facilitate testing blood for specific disease biomarkers.