Background: Thymosin α₁ (Tα₁), a synthetic version of a thymic-derived biological response modifier was the first of the thymosins in clinical use. Tα₁ is approved in over 35 countries for the treatment of hepatitis B and C, and as an immune stimulant and adjuvant. Tα₁ is also in late-stage clinical testing in the United States and Europe for hepatitis C and stage IV melanoma. Objective/methods: Novel applications and other recently completed trials point to much broader clinical applications of Tα₁ in the treatment of life-threatening and chronic diseases, and are the subject of this review. Result/conclusions: The most recent reports of clinical trials with Tα₁ are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients. It is also emerging as a promising chemoprotection agent in patients undergoing chemotherapy.