Following intracerebral hemorrhage (ICH) there is a sequential response involving activation of the coagulation cascade/platelet plug formation, vascular repair, upregulation of endogenous defense mechanisms and clot resolution. How these responses are coordinated and modified by different hematoma sizes has received little attention. This paper reviews evidence that thrombin can modulate and may coordinate the components of the endogenous response. This has potential consequences for treatment of ICH with a number of modalities.