Exposure to traumatic events is common. While many individuals recover following trauma exposure, a substantial subset develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as posttraumatic stress, major depression, and regional or widespread chronic musculoskeletal pain. APNS cause substantial burden to the individual and to society, causing functional impairment and physical disability, risk for suicide, lost workdays, and increased health care costs. Contemporary treatment is limited by an inability to identify individuals at high risk of APNS in the immediate aftermath of trauma, and an inability to identify optimal treatments for individual patients. Our purpose is to provide a comprehensive review describing candidate blood-based biomarkers that may help to identify those at high risk of APNS and/or guide individual intervention decision-making. Such blood-based biomarkers include circulating biological factors such as hormones, proteins, immune molecules, neuropeptides, neurotransmitters, mRNA, and noncoding RNA expression signatures, while we do not review genetic and epigenetic biomarkers due to other recent reviews of this topic. The current state of the literature on circulating risk biomarkers of APNS is summarized, and key considerations and challenges for their discovery and translation are discussed. We also describe the AURORA study, a specific example of current scientific efforts to identify such circulating risk biomarkers and the largest study to date focused on identifying risk and prognostic factors in the aftermath of trauma exposure.