Severe traumatic brain injury (STBI) is a pervasive disease that disproportionately affects young patients, elderly patients, and patients who were previously healthy. The neurologist’s roles in treating STBI are multiple, ranging from involvement in the acute critical care setting to managing the chronic sequelae that affect patients with STBI and their families. The search for effective treatments for STBI continues despite many so-called negative clinical trial results. To date, no generalizable therapy or intervention has proven to improve outcomes after STBI. In this Viewpoint, we discuss previously underrepresented factors crucial to making progress in STBI research: using precision medicine to design intervention trials and standardizing critical care management of patients with STBI, focusing specifically on differences in prognostication and withdrawal of life-sustaining therapy (WLST). Despite a historical lack of successful trials, we urge optimism because the future of clinical research in STBI is rich with opportunity.