Hepatic de novo production of glucose and oxidation of fatty acids (FA) are critical in supporting milk production during the transition to lactation period. During this period of metabolic challenge, there is an increase in FA taken up by the liver. Although the optimal fate for these FA is complete oxidation through the TCA cycle, alternative fates include incomplete oxidation via ketogenesis or storage within the liver as triglycerides (TG). Influencing the relative capacity of these pathways may prevent ketosis and fatty liver and improve hepatic efficiency. Hepatic nutrient partitioning reflects complex regulation of key enzymatic steps modulated by FA, substrates, and methyl donors. Fatty acids mobilized from adipose tissue have regulatory effects on genes such as pyruvate carboxylase; however, both in vivo and vitro work suggests there may be other influences present which can result in differential regulation between cows that subsequently develop sub-clinical ketosis and that some FA may be preferentially stored or oxidized. Supporting TG export or subsequent lipolysis is also important for minimizing liver TG accumulation. Although there is biochemical overlap between choline and methionine within both methyl donor metabolism and cellular lipid packaging, there is evidence that each of these nutrients have their own metabolic priorities. Increased FA oxidation and TG export with choline treatment may support both decreased cellular TG and ketone body secretion. Together, these shifts in pathway flux may also support the increased cellular glycogen observed in vitro and give reason to further examine gluconeogenic capacity in cows supplemented with choline. While further research is needed to continue refining our understanding of the intricate balance that regulates hepatic metabolism, shifting nutrient partitioning via oxidative pathways may be key in supporting both efficiency and metabolic health.