Helena Ivanovna of Moscow was daughter of Ivan III the Great, Grand Prince of Moscow, and an uncrowned Grand Duchess of Lithuania and Queen of Poland as she would not convert from Eastern Orthodoxy to Catholicism. Her childless marriage to Grand Duke of Lithuania and later King of Poland Alexander Jagiellon was a constant source of tension between the Grand Duchy of Moscow and the Grand Duchy of Lithuania. Instead of guaranteeing peace, Helena's marriage gave her father Ivan III an excuse to interfere in Lithuanian affairs accusing Alexander of mistreating Helena and repressing Orthodox believers. This became the pretext to renew the Muscovite–Lithuanian Wars in 1500. The war ended with a six-year truce in 1503; the Grand Duchy of Lithuania lost about a third of its territory. Despite political tensions and religious differences, the marriage was a loving one and the royal couple was close. After her husband's death in 1506, Helena wanted to return to Moscow but was not allowed. When she planned to run away, she was arrested and reportedly poisoned.

Barbara Zápolya was Queen of Poland and Grand Duchess of Lithuania as the first wife of King Sigismund I the Old from 1512 to 1515. Marriage to Barbara represented an alliance between Sigismund and the House of Zápolya against the Habsburgs in succession disputes over the throne to the Kingdom of Hungary. The alliance was short-lived as the renewed Muscovite–Lithuanian War forced Sigismund to look for Habsburg allies. The marriage was loving, but short. Barbara was the mother of Hedwig, Electress of Bradenburg, but died soon after the birth of her second daughter Anna.