This paper reviews recent data and concepts on the development of inflammation in the reproductive tract of dairy cows during the first 2 months after calving. The incidence of metritis is typically 10–20%, with 5–15% of cows having purulent vaginal discharge (PVD), 15–40% having cervicitis approximately 1 month after calving, and 10–30% having cytological endometritis between 1 and 2 months after calving. Endometritis, cervicitis and PVD are distinct conditions, each of which is associated with significantly increased time to pregnancy, and affected cows often have more than one of these conditions. Cumulatively, 35–50% of cows have at least one form of pathological reproductive tract inflammation between 3 and 7 weeks postpartum. It is hypothesized that reproductive tract disease represents a failure of the immune system to switch fast enough or far enough from the down-regulated state necessary for maintenance of pregnancy to a heightened state of function for postpartum clearance of bacteria and tissue debris and then to a ‘quiet’ state 3–4 weeks later. There are numerous links between fat metabolism, inflammation and immune function, and changes in these precede reproductive tract disease by several weeks. An excessive pro-inflammatory state early in the postpartum period appears to be a key feature of cows with endometritis approximately 1 month later. Generally, worse postpartum negative energy balance (NEB) is associated with more severe or prolonged uterine inflammation. Aspects of both mononuclear cell proliferation and neutrophil oxidative burst are commonly impaired, particularly in association with elevated non-esterified fatty acid concentrations and to a lesser degree by ketosis. In summary, NEB contributes to immune dysfunction which in turn is a major component of reproductive tract inflammatory disease. The factors that initiate and sustain harmful inflammation of the reproductive tract are not yet well quantified.