The mineral and energy imbalances of the transition period of dairy cows have a negative impact in the dairy industry because they are prevalent, contribute to economic losses and are an animal welfare issue. This dissertation aimed to advance our understanding of the physiological adaptations characteristic of this period. A series of experiments were conducted to: advance the understanding of body reserves mobilization around parturition, characterize the dynamics of blood calcium concentration after calving and evaluate its association with reproductive performance, and advance the understanding of the regulation of fibroblast growth factor 21 in the dairy cow. Chapter 2 reviews the current information available regarding the physiological adaptations necessary to overcome the mineral and energy challenges faced by dairy cows in the periparturient period, with an emphasis in subclinical hypocalcemia and fibroblast growth factor 21. In Chapter 3, it is reported that blood calcium concentration is the lowest in the first day post-partum, independently of parity, but normal levels are regained by day 3 of lactation. Additionally, the interaction between subclinical hypocalcemia, disease occurrence, and increased levels of metabolites surrogates of negative energy balance significantly influence the loss of body weight in parity > 3 animals. Chapter 4 introduces a new concept of subclinical hypocalcemia that considers not only the blood calcium concentration at a given time but also how many days post-partum blood calcium concentration is below the established cut-off point. In this chapter, it is reported that approximately 1/3 of the dairy cows have low blood calcium concentration during the first 3 days in lactation. Additionally, chronic subclinical hypocalcemia was associated with impaired reproductive performance of these animals. Chapter 5 aims to identify objective measurements to assess body condition in dairy cows. In this chapter, sequential measurement of body weight and the measurement of back-fat thickness were compared to the traditional visual body condition scoring system. It was determined that body weight has the potential to be used to predict milk production throughout lactation, but other variables (i.e. disease and negative energy balance) can significant interfere with this measurement and further investigation of this methodology is necessary prior to the diffusion of this technique through the dairy industry at large. Finally in Chapter 6, we demonstrated the importance of elevated plasma non-esterified fatty acids in hepatic fibroblast growth factor 21 production and consequently the increased circulating levels of this this hormone. In summary, this dissertation contributes to the current knowledge regarding various aspects of dairy cows adaptation to milk production. Nonetheless, further research is needed to advance our knowledge on the epidemiology of subclinical hypocalcemia and its influence in production outcomes. As well as to better understand the effects of elevated fibroblast growth factor 21 concentrations in early lactation dairy cows.