Many of the diseases that affect dairy cattle either in confinement or pasture-based systems typically occur in the first two months of lactation, before the first postpartum insemination. The increased susceptibility to metabolic and infectious diseases with parturition and the onset of lactation poses a major challenge to reproduction. A wealth of information in the scientific literature is available linking diseases with depressed reproduction in dairy cows. Unfortunately, only few studies have established a causal relationship between a specific disease and fertility, and little is known about the mechanisms that underlie the decrease in pregnancy in dairy cows that had disease in early lactation. It is clear that dairy cows that suffer from disease processes have impaired resumption of postpartum ovulation, compromised fertilization and preand peri-implantation conceptus development, altered conceptus gene expression, increased pregnancy loss and, ultimately reduced pregnancy per insemination that causes an extension in time to pregnancy. Because mechanisms are poorly understood, no target intervention is available at this time to reverse the poor reproduction in cows that develop periparturient diseases, except methods to induce cyclicity in anovular cows or to improve insemination rate in cows not detected in estrus. Regardless of a better understanding of the underlying biology of poor fertility in diseased cows, a pivotal approach is to implement strategies that mitigate the risk factors that predispose cows to disease. Such interventions include, but are not limited to, improving transition cow management and grouping, proper dietary formulation to prevent periparturient diseases associated with intermediary and mineral metabolism, strategies for reducing calving-related disorders, and methods to prevent mastitis and lameness. Future developments in target strategies to improve reproduction of cows suffering from peripartum diseases will require a better understanding of the impaired biological processes that compromise establishment and maintenance of pregnancy in this subfertile population of cows