In the field of traumatic stress, chemoprophylaxis is a term that is often used but rarely well understood. There has been no shortage of debate on the issue, but few rigorous studies to ground the discussion. The purpose of the current paper is to explore the issues surrounding this contentious area. Databases including PubMed, PsychArticles and Web of Knowledge were searched using the key words 'chemo or pharmaco', 'prevention or prophylaxis', and 'PTSD or post-traumatic stress'.