The nature of warfare in the 21st century has led to a significant increase in primary blast or over-pressurization injuries to the whole body and head, which manifest as a complex of neuro-somatic damage, including traumatic brain injury (TBI). Identifying relevant pathogenic pathways in reproducible experimental models of primary blast wave exposure is therefore vital to the development of biomarkers for diagnostics of blast brain injury. Comparative analysis of mechanisms and putative biomarkers of blast brain injury is complicated by a deficiency of experimental studies. In this article, we present an overview of current TBI biomarkers, as well as outline experimental strategies to investigate molecular signatures of blast neurotrauma and to develop a pathway network map for novel biomarker discovery. These biomarkers will be effective for triaging and managing both combat and civilian casualities.