In 1570, Queen Elizabeth I was famously excommunicated by Pope Pius V. The bull, known after its opening line, Regnans in excelsis (“He who reigns in the highest place”), became a powerful tool of anti-Catholic propaganda for the regime and it served as a catalyst for harsh measures against English Catholics. Three contextual aspects of the publication of the bull that are explored here have been ignored or misunderstood. First, the bull was produced by a reinvigorated church, which was applying the reforms envisaged at Trent. Second, the queen of England was denounced by some of her subjects whose depositions have received little attention and the case against her was solidly grounded in Catholic understandings of the papal powers of excommunication and deposition. Third, Philip II of Spain’s refusal to implement the bull was founded on pragmatic reasons prompted by his displeasure at not being mentioned in the bull.