Coffee and beverages with caffeine represent one of the world’s leading commodities. This chapter presents the major epidemiological and clinical trials that have examined the association between coffee or caffeine consumption and serum lipid and lipoprotein concentrations. In addition, it discusses the various in vitro and in vivo studies to identify the mechanisms by which coffee might increase serum lipid and lipoprotein concentrations. About 32 epidemiological studies have reported an association between coffee intake and serum cholesterol concentrations. A number of studies have been performed to determine whether different coffee brewing methods have an effect on serum cholesterol concentrations. The clinical trials have an advantage over epidemiological studies in that the amount of coffee consumed is more precisely known and that potential confounder variables are controlled. A number of clinical studies have shown that two diterpenes in coffee—cafestol and kahweol—can cause an increase in serum lipid and lipoprotein concentrations.