Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable tissue adhesive or sealant to stop or control bleeding or provide air and fluid tightness in many surgical situations. This review describes the historical development of current fibrin sealant preparations and the scientific rationale behind the alleged physiological benefits of its major plasma-derived components. A comparison in the extraction methods and viral reduction treatments applied to current commercial products and autologous preparations, and their respective advantages and limits, are discussed. Application devices used for surgical applications are described. A survey of the major clinical applications in various surgical areas is presented. Current issues in terms of viral safety, definition of optimal fibrin sealant composition, and regulatory concerns, especially to demonstrate clinical efficacy, are also included.