Studies in various animal models of disease and repair with thymosin beta(4) (Tbeta(4)), the major actin-sequestering molecule in mammalian cells, have provided the scientific foundation for the ongoing dermal, corneal, and cardiac wound repair multicenter clinical trials. Tbeta(4) has of multiple biological activities, which include down-regulation of inflammatory chemokines and cytokines, and promotion of cell migration, blood vessel formation, cell survival, and stem cell maturation. All of these activities contribute to the multiple wound healing properties that have been observed in animal studies. This paper reviews and discusses the topical and systemic uses of Tbeta(4) in various animal models that demonstrate its potential for clinical use.