The recent advances in proteomics, improved to MS-based shotgun proteomics, permit the large-scale analyses, and detection and validation of differentially expressed proteins as potential biomarkers of physiopathological states. This approach is supported by the development of high-throughput technologies combined with powerful computational and bioinformatics tools. These aspects, translating proteomics in clinical applications, allow the correlation of protein expression to biological processes and are defined as Clinical Proteomics. In this chapter, an overview is given on Clinical Proteomics for Boron Neutron Capture Therapy (BNCT), describing useful samples and their preparation, the actual examples and perspectives useful for improving applications of BNCT, as a contribution to Personalized Medicine, focused on risk assessment, prevention, early diagnosis, and proper treatment for everyone. The combination of noninvasive samples with shotgun proteomics, integrated by network analysis, is contributing to the development of a Clinical Proteomics strategy, involving the characterization of biomarkers and perturbed molecular pathways in relation to disease states. BNCT can take advantage of clinical proteomics to understand the biochemical and physiological issues, including the molecular mechanisms related to therapeutic effects (so-called endotype approach). In the near future, this strategy will permit the monitoring of therapeutic efficacies and the identification of disease- and therapy-related pathways.