Thrombocytopenia is common in chronic liver disorders, and may be due to a variety of non-immune and immune mechanisms. The latter include clearance of immune complexes, or increased platelet sequestration driven from an antigen-antibody immune response. A number of case observations led to the assumption that autoimmune thrombocytopenia (AITP) is a common feature in HCV infected individuals, while it is rare in non-immune chronic liver disease. Clinically, the differentiation of AITP from other forms of thrombocytopenia can influence therapeutic measures. Therefore, in HCV infection it is mandatory to disclose the pathomechanisms of thrombocytopenia in each case individually. In this article we will discuss the various pathomechanisms that may result in thrombocytopenia in HCV infection, review the current literature with reference to an increased occurrence of AITP in HCV infected patients, and how laboratory tools may assist in the diagnosis. Finally, we will address some of the questions that need to be answered to get a clearer impression of laboratory and clinical parameters pertaining to a possible association of AITP in HCV.