This paper will review the historical background that has generated our present interest in the actions of the thymosins in biological therapy. It will also discuss the multiple actions of the thymosins in the immune, endocrine and central nervous systems. The isolation from the thymus gland of the thymosins, a family of biologically active molecules with hormone-like properties, was first described in 1966 by AL Goldstein and A White. Since that time, significant progress has been made in understanding the role of the thymosins in immunity and the nature of the growth factors, cytokines and chemokines they modulate. The thymosins include a family of biochemically and functionally distinct polypeptides with clinically important physiological properties. In the early 1970s, preclinical studies establishing the immunorestorative effects of a partially purified thymosin preparation termed thymosin fraction 5 (TF5) provided the scientific foundation for the first clinical trials with TF5 in 1974. TF5 was effective in turning on the immune systems of a number of children with DiGeorge syndrome and other thymic dysplasias. These trials led to further interest in the active components in TF5 and to the chemical characterisation of the biologically active thymosins. Several of these molecules are showing significant promise in the clinic in the areas of cancer, infectious diseases and wound healing.