A perspective overview is given describing the current development of multiplex mass spectrometry assay technology platforms utilized for high throughput clinical sample analysis. The development of targeted therapies with novel personalized medicine drugs will require new tools for monitoring efficacy and outcome that will rely on both the quantification of disease progression related biomarkers as well as the measurement of disease specific pathway/signaling proteins.The bioinformatics developments play a key central role in the area of clinical proteomics where targeted peptide expressions in health and disease are investigated in small-, medium- and large-scaled clinical studies.An outline is presented describing applications of the selected reaction monitoring (SRM) mass spectrometry assay principle. This assay form enables the simultaneous description of multiple protein biomarkers and is an area under a fast and progressive development throughout the community. The Human Proteome Organization, HUPO, recently launched the Human Proteome Project (HPP) that will map the organization of proteins on specific chromosomes, on a chromosome-by-chromosome basis utilizing the SRM technology platform. Specific examples of an SRM-multiplex quantitative assay platform dedicated to the cardiovascular disease area, screening Apo A1, Apo A4, Apo B, Apo CI, Apo CII, Apo CIII, Apo D, Apo E, Apo H, and CRP biomarkers used in daily diagnosis routines in clinical hospitals globally, are presented. We also provide data on prostate cancer studies that have identified a variety of PSA isoforms characterized by high-resolution separation interfaced to mass spectrometry.