Enhancing longevity by reducing involuntary culling and consequently increasing productive life and lifetime production of dairy cows is not only a strategy to improve a farm’s profit, but is also related to improved animal welfare. High rates of involuntary culling in dairy cows are currently attributed to fertility problems, mastitis and locomotive disorders. Disease incidence is high in particular in the early-lactation period. The high disease incidence in early lactation has been attributed to metabolic stress related to the high metabolic priority for lactation and the inability of the cow to adapt effectively to the new lactation. Several biological mechanisms interact in the peripartum period of dairy cows and can result in this inability to adapt effectively to lactation. Biological mechanisms reviewed are metabolic adaptation, oxidative stress, immune function and inflammation, and feed intake capacity. Although relationships between these mechanisms become increasingly clear, these relationships are complex and not yet completely understood. Appropriate management of dairy cows in the peripartum period can facilitate cows to adapt to a new lactation. Nutritional and management strategies to ease adaptation are divided into strategies to restrict energy intake in the dry period, to improve energy intake in early lactation, alter repartitioning of energy between milk and body tissue, and strategies to support fat or carbohydrate metabolism. The success of various strategies, however, is often hampered by the complexity ofinteractions and high between-cow variation. We advocate for a multidisciplinary approach tounderstand and manage adaptation to a new lactation aiming at an improvement of cow welfareand longevity.