Of her five children, only three survived her

Isabella, John, Joanna, Maria, and Catherine were the couple's five children. Her sole son and heir Juan died in 1497; her daughter Isabella, queen of Portugal, died in childbirth in 1498; and her grandchild Miguel, who would have brought about a personal union between Spain and Portugal in 1500, all occurred during the last ten years of her reign. Only three of her five children - Joanna and Catherine being one - lived past Isabella's passing, which is one of the most interesting facts about Isabella I of Castile.

Instead, her daughter Joan, who was Philip I's bride and gave birth to Charles V, the Holy Roman Emperor, inherited Castile. However, the queen found little solace in this as Joan had already begun to exhibit symptoms of the mental disorder that would later win her the nickname "the Mad" by 1501. Following the death of Prince Arthur of Wales, Catherine of Aragon wed his brother, King Henry VIII of England. Isabella became Mary I of England's grandmother through Catherine's marriage.