Evidence indicates that post-traumatic stress disorder (PTSD) is a significant risk factor for the development and progression of cardiovascular disease (CVD). Most explanations for PTSD-CVD associations conceptualize PTSD as a stress-related mental health disorder that elicits physiological, behavioral, and psychological responses that are causal factors in the development of cardiovascular disorders. This article reviews evidence for the broader physical health consequences of PTSD, and presents a conceptual model based on research suggesting that PTSD is a systemic disorder. Specifically, research findings indicate that diagnostic criteria are just the “tip of the iceberg” of a broader systemic disorder with elements that are cardiovascular risk factors. These systemic physiological and behavioral elements therefore should not be regarded as accompanying but unrelated diseases or comorbidities, but as inherent components of PTSD that directly impact the development of CVD. The systemic disorder approach has implications for the conceptualization of PTSD as a cardiovascular risk factor, for needed research on PTSD and CVD, and for clinical efforts to reduce PTSD-associated cardiovascular risk. It is suggested that treatments that aim to reduce cardiovascular disease risk need to address both the PTSD diagnostic components and its associated cardiovascular risk factors. Further research is needed to test the applicability and implications of the systemic disorder perspective.