1522–86, Spanish regent of the Netherlands; illegitimate daughter of Holy Roman Emperor Charles V. She was married (1536) to Alessandro de' Medici (d. 1537) and (1538) to Ottavio Farnese, duke of Parma. Appointed Spanish governor of the Netherlands (1559), she was restricted in her authority by a council of state headed by Cardinal Granvelle. Charged with the difficult task of carrying out the religious policy of her half brother Philip II of Spain, she urged and finally secured the recall of the unpopular prelate. She subsequently showed favor to the national party, but after the outbreak of violence she turned against the popular leaders (Egmont, Hoorn, and William the Silent). In 1567 the duke of Alba arrived at Brussels to suppress the opposition by force. Margaret warned Philip II against harsh measures and resigned as regent, being unable to agree with Alba. She was a woman of great ability and firmness, and her resignation was generally regretted. Margaret's son was the noted general Alessandro Farnese, duke of Parma and Piacenza.

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