This troubled period in Agen's history was followed by a rebirth that was primarily intellectual under a succession of Italian-born bishops, but was also commercial as Agen became the centre for exporting products such as wine, flour and prunes from its rich agricultural hinterland.
Arts and Sciences flourished under the Italians, with many well-known Renaissance figures (Nostradamus, for example), being linked with the town. 
This brilliant era was brought to a halt by the Wars of Religion. Agen came under the influence of its smaller neighbour, Nérac, where Marguerite d'Angoulème, Queen of Navarre, supported the Protestant cause. Agen, though, stayed faithful to the Catholic Religion and to the King of France. The Protestants took the town twice, only for the Catholic armies under Blaise de Monluc to regain control. 
The region was devastated by the successive sieges and occupations, which brought pillage, massacres and the destruction of religious buildings in their wake. 

In 1598, the Edict of Nantes removed all social restrictions from the Huguenots and the region returned to a relative calm.