This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism in Mannheim, Germany, in October 2004. This symposium was dedicated to Charles S. Lieber in recognition of his contribution in alcohol research over the last 50 years. It was divided into two parts, namely effects of alcohol on the gastrointestinal tract and effects of alcohol on the liver. Major emphasis was given to recent discoveries elucidating mechanisms of alcohol-associated carcinogenesis. M. Salaspuro (Finland) discussed the role of acetaldehyde in the saliva and in the large intestine with respect to its role in the pathogenesis of alcohol-associated cancer, and H. K. Seitz (Germany) presented new data identifying individuals homozygous for the ADH1C&1 allele as high on risk for alcohol-associated upper aerodigestive tract cancer. M. Savolainen (Finland) discussed the role phosphatidylethanol as a bioactive lipid that can mediate beneficial and harmful effects of alcohol drinking. In the second part of the symposium, alcoholic liver disease was discussed. P. Haber (Australia) presented new data on hepatic transcriptome in alcoholic liver disease with the identification of new genes possibly involved in alcohol-initiated fibrogenesis of the liver, and H. Moshage (The Netherlands) described survival mechanisms of the cholestatic hepatocytes with implications for therapy in cholestatic liver disease. The role of the hepatic microsomal ethanol oxidizing system in the metabolism of alcohol in alcoholic liver disease was summarized by R. Teschke (Germany). H. Ishii (Japan) discussed the current status and treatment of alcoholic hepatitis in Japan. Finally, in a state-of-the-art lecture, Charles S. Lieber (USA) discussed the development of the understanding of the pathophysiology of alcoholic liver disease in the last 50 years. He emphasized the role of pathophysiology as an important prerequisite for better treatment strategies.