The objective of this report is to review the literature on elevated blood concentrations of nonesterified fatty acids (NEFA) before and after parturition in high-yielding dairy cows. It highlights the factors that influence serum NEFA production and their circulation before and after parturition, such as adaptation for nutrient partitioning for fetal needs, onset of lactogenesis, stress of calving and numerous changes in physiological, metabolic, and endocrine status to accommodate parturition and lactogenesis. The role of NEFA in the liver and peripheral tissues and its toxic effects when in excess are discussed. The cow's adaptive physiologic mechanisms to prevent or decrease excessive values of serum NEFA and preventive and therapeutic interventions to enhance these mechanisms are categorized as natural and artificial antidotes respectively. Feeding systems during the dry period and daily exercise or walking activity which may burn excessive NEFA through beta-oxidation in the muscles are considered as more useful antidotes to managing the NEFA metabolism. This will minimize accumulation of lipids in the liver during early lactation and alleviate the negative effects of plasma NEFA leading to more optimal metabolic health and productivity of dairy cows.