•Between 2007–2015, out of the one million combat veterans screened for traumatic brain injury (TBI), 8.4% of these Veterans received a diagnosis of TBI after comprehensive evaluation, the majority are characterized as mTBI/Concussion (mTBI) and, in great proportion, related to blast exposures.•Mild traumatic brain injury called ‘a signature injury’ also known as ‘the invisible injury’ of war received increased attention during current conflicts.•Specific clinical and research challenges in mTBI include identification and assessment of neuropathological, cellular and resulting cognitive, emotional, behavioral and neurological consequences.•Enhanced research support for understanding TBI promises opportunities for advances in its diagnosis, management as well as for understanding pathogenesis of degenerative brain disease and other brain related disorders. Between April 2007 and December 2015, the Veterans Health Administration (VHA) screened one million combat veterans for traumatic brain injury (TBI), among 2.6 million deployed during operations Enduring Freedom, Iraqi Freedom and New Dawn (OEF/OIF/OND). Since 2007, among those reporting, screened and referred for definitive evaluation, approximately 8.4% of these Veterans received a diagnosis of TBI, the majority characterized as mTBI/Concussion (mTBI) and, in great proportion, related to blast exposures. Mild Traumatic brain injury called “a signature injury” is also known as ‘the invisible injury’ of these conflicts. Identifying and assessing neuropathological, cellular and resulting cognitive, emotional, behavioral and neurological consequences of mTBI comprise vast clinical and research challenges. We provide a brief overview of current history, injury mechanisms related to blast exposure, coordinated research support, and the need to understand specific cellular and neurological changes occurring with blast injury, particularly mTBI.