Against All Heresies was written at the request of Spanish merchants of Flanders to combat heretics and was first published in Paris in 1534. It is a description and criticism of more than 400 heresies, which had arisen in the Church since the time of the Apostles, presented in alphabetical order. It was the author's most popular work for which he received the nickname, "the scourge of heretics." King Philip II of Spain, whom the author served as chaplain, wrote in the preface of this work that this book is "such a useful and beneficial book for the Christian state." St. Robert Bellarmine drew from it in writing his Controversies.

The author, Alphonsus a Castro, born at Zamora, Spain, was admitted into the Order of St. Francis at Salamanca. He was one of the most celebrated preachers of his time; and his merit procured him the esteem of Charles V and Philip II. He attended Philip II when that prince went to England to marry the queen. Afterwards he made a long stay in the Low Countries; and he was there still when the king of Spain nominated him to the Archbishopric of Compostella. But before he received his Bulls, he died at Brussels the 15th of February, 1558, at sixty-three years of age. Alfonso García Matamoros in his De academiis et doctis viris Hispaniae wrote that de Castro fought with heretics, whom he refuted very strongly and eloquently, such that he strengthens our faith ornately and copiously, and he does not hesitate to compare him "with many preeminent authors of antiquity in fact in points of doctrine."

The book is a reasoned invitation to conversion to Catholicism, the endeavor of a preacher theologian systematically doing a pastoral work. It is the endeavor that justifies its numerous republications due to the timeliness of the work. It is certain that the Catholic world then greatly approved of this book, even to the point of constituting it as a manual for theologians and for Catholic apologists. And that this was not exaggerated, is shown by the fact that still today it constitutes a major monuments of positive theology for its abundance of facts, and Scriptural and Patristic doctrine accumulated in its pages. This abundance of positive doctrine is so much the more marvelous because in the time in which it was written, the works of the Church Fathers were so little known. How and where could Father Castro collect that barrage of quotations which fill the pages of his work? The argument that best reveals the universal acceptation is the number of its editions. It went through twenty editions between 1534 and 1568, making it the all-time most printed inquisitional treatise, and the main publishing houses of Europe took interest in publishing it.