Rising as a political power in the early sixteenth century, the Safavids were able to mobilize people from Azerbaijan, Iraq, Syria and Anatolia. Sultans Selim (r. 1512–1520) and Süleyman’s (r. 1520–1566) military undertakings brought most of Anatolia under the Ottoman military and administrative control, but many Qizilbash people from the Ottoman territories maintained their “affiliation” with the Safavids. This paper investigates the religio-legal opinions of Sarıgörez Nureddin Hamza (d. 1522), Kemalpaşazade (d. 1534) and Ebussuud (d. 1574) about the Safavids and the Qizilbash. Sarıgörez and Kemalpaşazade drew up their pieces in 1514, while Ebussuud wrote down most of his opinions in the late 1540s and 1550s. Historians have hitherto tended to see these writings as uniform political documents, intended to justify both fighting against the Safavids and the unhindered persecution of Ottoman Qizilbash subjects. However, examination of these opinions with particular attention to their religio-legal content reveals differences; no two authors agree on all views about this issue. Generally speaking, among the reasons for their disagreement are different perceptions of the gravity of the Safavid and Qizilbash threat, changes in the preference of applicable jurisprudential doctrine and the interpretation of the jurisprudential concepts and shifts in socio-political conditions. All the jurists under study justify fighting against the Safavids; however, they differ in the evaluation of the religio-legal situation of Ottoman Qizilbash subjects. For example, Sarıgörez provides the Ottoman executive authorities with religio-legal arguments to persecute the supporters of the Safavids everywhere, including the Ottoman territories; Kemalpaşazade prohibits the persecution of Ottoman Qizilbash subjects; finally, Ebussuud emphasizes the primacy of the Sultan’s decision, proposes lenient treatment of Ottoman Qizilbash subjects and opens the way for their integration to the Ottoman society. It is possible to say that the analysis of these three religio-legal opinions sheds light not only on the treatment of the Safavids and Qizilbash but also on the nature of juristic authority and its position vis-à-vis the government in the Ottoman Empire.