The cow is notable among the domestic species for the almost ubiquitous bacterial contamination of the uterine lumen after parturition and the high incidence of clinical uterine disease. Such uterine disease not only disrupts uterine tissues, but also ovarian follicle growth and function by perturbation of the hypothalamus, pituitary, and ovary. Other events such as the postpartum negative energy balance also have similar multilevel effects on postpartum endocrinology. Return of ovarian cyclical activity is dependent on the innate immune system resolving uterine bacterial contamination,prompt uterine involution, and a short interval to the negative energy balance nadir. Although the risk factors for uterine disease have been described, preventive strategies are not widely adopted. Thus, veterinarians must identify and treat uterine disease efficiently to limit their negative effect on fertility.