Platelet-rich plasma (PRP) has recently become the focus of intensive interest and discussion, in part because of the expanding understanding of platelet function. Anucleate platelets within PRP release a myriad of growth factors and cytokines while contributing to plasma coagulation and fibrin development; the latter acts as vehicle for the local delivery. The biological effects of PRP are largely attributed to the platelet secretome and plasma signaling proteins. Clinical data suggest that PRPs may exploit different regenerative mechanisms under diverse disease conditions, including hemostasis, inflammation, angiogenesis and the synthesis of extracellular matrix. The success of PRP therapies depends on current tissue healing research and the translation of this knowledge into clinical developments.