Most of the metabolic diseases of dairy cows-milk fever, ketosis, retained placenta, and displacement of the abomasum-occur within the first 2 wk of lactation. The etiology of many of those metabolic diseases that are not clinically apparent during the first 2 wk of lactation, such as laminitis, can be traced back to insults that occurred during early lactation. In addition to metabolic disease, the overwhelming majority of infectious disease, in particular mastitis, becomes clinically apparent during the first 2 wk of lactation. Three basic physiological functions must be maintained during the periparturient period if disease is to be avoided: adaptation of the rumen to lactation diets that are high in energy density, maintenance of normocalcemia, and maintenance of a strong immune system. The incidence of both metabolic and infectious diseases is greatly increased whenever one or more of these physiological functions are impaired. This paper discusses the etiological role of each of these factors in the development of common diseases encountered during the periparturient period.