Numerous studies have documented that orthopedic trauma patients’ experience long-term disability, even after complete clinical recovery. For many patients, the level of disability is not fully explained by the extent and severity of their injuries. These studies have also identified risk and protective factors that may explain why some patients experience full recovery while others suffer from life-long disability. Key factors that may play a central role as both predictors and mediators of disability are pain, depression, and anxiety, and posttraumatic stress disorder (PTSD). Anxiety, which in this population can take the form of acute and PTSD, has gained particular attention in the past few decades and is the subject of intense study, particularly among veteran populations and those experiencing life-threatening injuries. Depression has been studied far longer and may constitute both a major risk factor preinjury and a detrimental factor in both the acute and long-term recovery phases. Pain has always been understood as a symptom of traumatic injuries, but is a focus of concern now also due to its role in the use of opioids and PTSD. In this manuscript we will briefly review the scope of the problem, discuss risk factors and potential intervention points, and broadly propose secondary prevention approaches suitable for implementation in the trauma setting, with a particular focus on the role of collaborative care models.