There are several candidate neuroprotective agents that have been shown in preclinical testing to improve outcomes following traumatic brain injury (TBI). Xiao and colleagues have performed an in hospital, double blind, randomized, controlled clinical trial utilizing progesterone in the treatment of patients sustaining TBI evaluating safety and long term clinical outcomes. These data, combined with the results of the previously published ProTECT trial, show progesterone to be safe and potentially efficacious in the treatment of TBI. Larger phase III trials will be necessary to verify results prior to clinical implementation. Clinical trials networks devoted to the study of TBI are vital to the timely clinical testing of these candidate agents and need to be supported. © 2008 BioMed Central Ltd.