Mules and hinnies are hybrid offspring of donkeys (Equus asinus) and horses (Equus caballus), with hinnies representing the reciprocal cross. Scientific knowledge about these hybrids is limited, especially regarding hinnies. While they are generally considered sterile, historical records, including references by Homer, describe fertile mules. Rare cases worldwide document mules and hinnies producing live offspring when mated with a jack.Hybrid sterility is primarily attributed to differences in chromosome number and structure, yet many hybrids still exhibit typical reproductive behaviors. Male mules, often castrated, may display aggression or produce spermatids if intact. Female mules and hinnies may show estrus behaviors, sometimes requiring ovariectomy to manage these behaviors. Beyond fertility, female hybrids have also been studied as recipients for equine embryo transfers, particularly for donkey embryos. Reciprocal crosses present additional reproductive challenges. Mares carrying mule foals may produce fewer endometrial cups, lower levels of equine chorionic gonadotropin (eCG), and reduced progesterone, all critical for maintaining pregnancy. Jennies mated to stallions may experience poor conception rates, potentially due to uterine immune responses to stallion versus jack semen. After birth, neonatal concerns include the risk of isoerythrolysis. With the growing interest in conserving donkey breeds and breeding mules for recreational or performance purposes, understanding the reproductive physiology, pregnancy management, and control of reproductive behaviors in these hybrids has become increasingly important.