The review outlines current models and evidence of biological models of complex PTSD. It commences with a critique of biological evidence of PTSD, incorporating work from animal and human models. It then discusses the role of neural factors underpinning treatment of PTSD, and how this may impact on complex PTSD. The issue of emotional regulation is discussed in the context of recent neuroimaging studies. Finally, these issues are contextualized in terms of DSM-5 and ICD-11 proposals for understanding complex PTSD. The review concludes that the field requires more rigorous research to both operationalize the definition of complex PTSD and its core mechanisms.