Joseph Nasi was born in Portugal as a marrano (practicing Judaism in secret), a son of the doctor Agostinho Micas (d. 1525), a well-known physician and professor at the University of Lisbon.
In 1561, Nasi backed Ioan Iacob Heraclid to rule as despot, supported Alexandru Lăpușneanu's return to the throne in place of Ștefan Tomșa (1564), and ultimately endorsed Ion Vodă cel Cumplit (1572);[7] he was himself considered a suitable choice for hospodar of either Moldavia or Wallachia in 1571, but Selim II rejected the proposal.
[10] Maintaining contacts with William the Silent,[11] Nasi encouraged the Netherlands to revolt against Spain, a major adversary of the Ottoman Empire (the rebellion was ultimately carried out by the Union of Utrecht, as the start of the Eighty Years' War).
[13] Nasi secured a grant giving ruling authority from the Sultan, and, with the assistance of Joseph ben Adruth,[12] rebuilt the walls and the town.
[12] Arrangements were made for Jews to move from the Papal States, but, when the Ottomans and the Republic of Venice went to war, the plan was abandoned.