Hepatitis C is one of the most common causes of chronic liver disease in Latin America. It is essential to understand the different mechanisms of transmission of the infection in order to design control measures. The pattern of transmission of the infection in our region suggests that the peak of the infection occurred 30 to 50 years ago. While most infections in Latin America seem to be the result of blood transfusion and unsafe therapeutic injection practices in the past, there is still a need to identify and notify infected blood donors. Intravenous drug use and sexually transmitted hepatitis C virus among human immunodeficiency virus-positive patients are current problems that need to be addressed.