The history and todays knowledge on the pathogenesis of arteriosclerosis emphasizing the importance of cholesterol concentration in plasma for the development of atherosclerosis is summarized. For proving the lipid hypothesis careful patient observation and new findings of molecular biology have added important information. More and more details on the complex interaction between risk factors, endothelial cells, smooth muscle cells, growth factors and the coagulation system are clarified. The increasing knowledge on the arteriosclerotic process has led to the fascinating situation, that for the first time in arteriosclerosis research causal approaches for therapy are under investigation.