Appropriate use of local hemostatic agent is one of the important factors on the prognosis of endodontic microsurgery. However, most investigations to date focus on the hemostatic efficacy of the agents, whereas their biologic characteristics have not received enough attention. The purpose of this paper was to review the biologic response of local hemostatic agents, and to provide clinical guidelines on their use during endodontic microsurgery. Electronic database (PUBMED) was screened to search related studies from 1980 to 2013, and 8 clinical studies and 18 animal studies were identified. Among the materials used in these studies, most widely-investigated and used materials, epinephrine, ferric sulfate (FS) and calcium sulfate (CS), were thoroughly discussed. Influence of these materials on local tissue and systemic condition, such as inflammatory and foreign body reaction, local ischemia, dyspigmentation, delayed or enhanced bone and soft tissue healing, and potential cardiovascular complications were assessed. Additionally, biological property of their carrier materials, cotton pellet and absorbable collagen, were also discussed. Clinicians should be aware of the biologic properties of local hemostatic agents and their carrier materials, and should pay attention to the potential complications when using them in endodontic microsurgery.