The repair of all tissue disruption begins with hemostasis and tissue sealing. Fibrin sealant is a concentrated mix of the factors required for the body to initiate this process. By applying this mixture directly to the site of injury, clotting and wound healing can be facilitated. Studies have demonstrated that fibrin sealant is effective in controlling bleeding and inducing tissue sealing in many organs. It is particularly useful in hepatobiliary surgery due to the soft nature of liver parenchyma and its propensity to bleed and leak bile. This chapter will discuss the basic science foundation of fibrin sealants and their applications in hepatic surgery.