Coordinated changes in energy metabolism develop to support gestation and lactation in the periparturient dairy cow. Maternal physiology involves the partitioning of nutrients (i.e. glucose, amino acids and fatty acids (FA)) for fetal growth and milk synthesis. However, the inability of the dairy cow to successfully adapt to a productive lactation may trigger metabolic stress characterized by uncontrolled adipose tissue lipolysis and reduced insulin sensitivity. A consequence is lipotoxicity and hepatic triglyceride deposition that favors the development of fatty liver disease (FLD) and ketosis. This review describes contemporary perspectives pertaining to FA surfeit and complex lipid metabolism in the transition dairy cow. The role of saturated and unsaturated FA as bioactive signaling molecules capable of modulating insulin secretion and sensitivity is explored. Moreover, the metabolic fate of FA as influenced by mitochondrial function is considered. This includes the influence of inadequate mitochondrial oxidation on acylcarnitine status and the use of FA for lipid mediator synthesis. Lipid mediators, including the sphingolipid ceramide and diacylglycerol, are evaluated considering their established ability to inhibit insulin signaling and glucose transport in non-ruminant diabetics. The mechanisms of FLD in the transition cow are revisited with attention centered on glycerophospholipid phosphatidylcholine and triglyceride secretion. The relationship between oxidative stress and oxylipids within the context of insulin antagonism, hepatic steatosis and inflammation is also reviewed. Lastly, peripartal hormonal involvement or lack thereof of adipokines (i.e. leptin, adiponectin) and hepatokines (i.e. fibroblast growth factor-21) is described. Similarities and differences in ruminant and non-ruminant physiology are routinely showcased. Unraveling the lipidome of the dairy cow has generated breakthroughs in our understanding of periparturient lipid biology. Therapeutic approaches that target FA and complex lipid metabolism holds promise to enhance cow health, well-being and productive lifespan.