R. Medina's personality and character emerge clearly from his many responsa. He imposed his authority on litigants by the power of his personality and succeeded in enforcing just compromises even when there was no basis for them in law. R. Medina was original in his method. He would give a decision in accordance with his own judgment when he found no precedent in the halakhot of his predecessors. Utterly fearless, he was alive to all problems which arose from the special circumstances of his time and place, and many of his responsa deal with the social and economic problems which exercised the minds of his contemporaries. R. Medina applied himself to the communal organization of the Spanish exiles, which he established on a solid juridical basis. In the controversies which reigned in Salonika and elsewhere as a result of the glaring gap between the rich and the poor, R. Medina maintained the right of the wealthy members of the community to regulate the direction of communal affairs. According to him it was not numbers but quality which counted and it was right that, as had been the custom in Spain, the leadership of the community should be in the hands of those who bear its financial burden, providing they were loyal to religious principles. With all his respect for local custom, he strove to make it accord with the halakhah as he saw it. Where that custom differed from that in force in Spain, he justified the latter on halakhic grounds and encouraged its gradual adoption, whether in the liturgical usage or in matters of shehitah, etc. Unlike his predecessors his consistency in this matter did not meet with great opposition. R. Medina's decisions with regard to anusim are important and are stamped with the same original approach as he showed in other matters for which there was no legal precedent. He regarded the community of Salonika and especially its educational institutions as being in a unique position, and as a result demanded a greater financial support for them than for the institutions in Erez Israel.
Side by side with his intensive halakhic activity R. Medina filled certain communal offices. He was the rabbi of the most important and largest congregations of Iberian communities in Salonika among them those of "Gerush" (i.e., of the exiles) and Lisbon, and went to Constantinople on missions on behalf of Salonika. He was called on to decide in the serious disputes which arose in Salonika and other communities, and succeeded in preventing schisms. His authority is seen in the fact that his signature appears on the majority of the communal regulations (haskamot) which have come down. Unlike many of his contemporaries of Spanish provenance R. Medina did not engage in Kabbalah, nor did he enter deeply into philosophy and secular studies. He was the man of halakhah and the communal leader par excellence. Despite his often unsatisfactory financial position he refused to take advantage of the exemption from taxes granted to scholars. Toward the end of his life legends were woven about him. R. Medina's responsa were published during his lifetime in two volumes (Salonika, 1585?–87) and an improved edition in three volumes (Salonika 1594–98). A considerable number also appear in the works of other scholars, while others are still in manuscript. Thirty of his sermons were published in Ben Shemu'el (Mantua, 1622) and his novellae on a number of tractates of the Talmud are still in manuscript.
בראש הספר הקדמה מאת נכד המחבר, ר' שמעיה ב"ר משה, המביא לבית הדפוס, ושני שירים. הראשון פותח: לך אלי בך חבלי היה לי שמעיה קול בחילי ממעונה. אוצר השירה והפיוט, ג, עמ' 37, מס' 801. השני: שיר נקרא לספר בן שמואל אשר הבין בשכלו זך מדינה. שם, עמ' 453, מס' 1003. דף קיז, א: שיר לשבח השלמת הספר: שלשים הדרושים את שמואל אשר עשה בספר זה שמואל.