Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardiac events is still debated. In addition to its historically well-defined interactions with central players of lipid metabolism, niacin can be processed by eukaryotic cells to synthesize a crucial cofactor, NAD(+). NAD(+) acts as a cofactor in key cellular processes, including oxidative phosphorylation, glycolysis, and DNA repair. More recently, evidence has emerged that NAD(+) also is an essential cosubstrate for the sirtuin family of protein deacylases and thereby has an impact on a wide range of cellular processes, most notably mitochondrial homeostasis, energy homeostasis, and lipid metabolism. NAD(+) achieves these remarkable effects through sirtuin-mediated deacetylation of key transcriptional regulators, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha, LXR, and SREBPs, that control these cellular processes. Here, we present an alternative point of view to explain niacin's mechanism of action, with a strong focus on the importance of how this old drug acts as a control switch of NAD(+)/sirtuin-mediated control of metabolism.