The hepatitis C virus (HCV) is a global public health problem, with chronic infection leading to development of cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). Treatment of HCV is suboptimal with overall response rates of slightly greater than 50% when patients are treated with pegylated interferon alfa and ribavirin. Thymosin alpha 1 (Talpha1; TA-1) is an immunomodulatory peptide with intrinsic activities that might improve treatment outcomes for HCV by incorporation of this agent in current treatment paradigms. An extensive body of literature supports a possible role for this agent in difficult to treat populations. However, clinical trials to date have failed to conclusively support the role of TA-1 in combination interferon-based therapies. Therefore, the promise of TA-1 adjunctive therapy for HCV remains, but the proof will require investment in large randomized clinical trials of appropriate patient populations.