Fibrin is a natural biopolymer involved in the coagulation cascade. It acts as a reservoir for growth factors, cells, and enzymes during wound healing and provides a scaffold for the synthesis of extracellular matrix. Thus, the use of fibrin has expanded in recent years from traditional use as a sealant for surgical applications, to a tissue engineering scaffold capable of providing nature's cues for tissue regeneration. This paper reviews the advantageous biological aspects of fibrin, the history of the scaffold material, and its present role in the delivery of drugs, growth factors, cells, and gene vectors. Examples are given of studies where the structure and form of the scaffold have been manipulated for optimal release of the therapeutic agent, optimal cellular activity, and investigation into stem cell differentiation. It is evident from the body of literature presented that the benefits of fibrin are being exploited for a vast range of tissue engineering applications and that fibrin remains a key scaffold material for the delivery of drugs and biomolecules.