The enzymatic processes by which the carbon chains of fatty acids are constructed have been a focus of biochemical research for over half a century, and more continues to be learned as X-ray crystallographic analyses provide increasingly detailed insight into the mechanisms by which these enzymes operate. In recent years there has been considerable interest in the role of these lipogenic enzymes in diabetes and obesity, as well as in the pathogenesis of cancer and as potential therapeutic targets in the search for new antitumor drugs. The latter has stemmed principally from numerous reports linking overexpression of several of the enzymes involved in de novo lipid biosynthesis with various human tumors and by recent advances in the structural biology of these key proteins. These enzymes include acetyl CoA carboxylase, fatty acid synthase, and ATP-citrate lyase, which operate in sequence and represent the primary linkage between carbohydrates and lipids in the cell's metabolic economy. The objectives of this Perspective are to (1) provide an overview of the lipogenic process, primarily as it relates to these three enzymes, (2) examine the relationship of lipogenesis to tumor biology, and (3) outline the opportunities and prospects for targeting the process in the search for new anticancer drugs.