Despite decades of laboratory research and clinical trials, a safe and effective 
treatment for traumatic brain injury (TBI) has yet to be put into successful 
clinical use. I suggest that much of the problem can be attributed to a 
reductionist perspective and attendant research strategy directed to finding or 
designing drugs that target a single receptor mechanism, gene, or brain locus. 
This approach fails to address the complexity of TBI, which leads to a cascade 
of systemic toxic events in the brain and throughout the body that may persist 
over long periods of time. Attention is now turning to pleiotropic drugs: drugs 
that act on multiple genomic, proteomic and metabolic pathways to enhance 
morphological and functional outcomes after brain injury. Of the various agents 
now in clinical trials, the neurosteroid progesterone (PROG) is gaining 
attention despite the widespread assumption that it is "just a female hormone" 
with limited, if any, neuroprotective properties. This perspective should 
change. PROG is also a powerful developmental hormone that plays a critical role 
in protecting the fetus during gestation. I argue here that development, 
neuroprotection and cellular repair have a number of properties in common. I 
discuss evidence that PROG is pleiotropically neuroprotective and may be a 
useful therapeutic and neuroprotective agent for central nervous system injury 
and some neurodegenerative diseases.