The failure of cows to successfully establish pregnancy after insemination is an important limiting factor for the efficiency of dairy production systems. The physiological reasons for this are many and pertain to the post partum and early pregnancy periods. Cows that suffer severe negative energy balance after parturition are prone to diseases (including uterine infection) that are, in part, explained by reduced function of the immune system, having negative consequences for subsequent fertility. In high-producing dairy cows, the duration and intensity of oestrus is low as a consequence of low circulating oestradiol concentrations, and after insemination, high embryo mortality is the single biggest factor reducing calving rates. Embryo mortality occurs as consequences of poor oocyte quality (probably caused by the adverse metabolic environment) and by poor maternal uterine environment (probably caused by carry-over effects of uterine infection and low circulating progesterone concentrations). Immediate improvements in the fertility of lactating cows on many farms can be achieved by applying existing knowledge, but longer-term sustained improvement will require additional knowledge in many areas including the physiology of the tissues that contribute to reproduction.