Jesaja Horowitz was chief rabbi in Frankfurt from 1609 to 1614 and lived in the house Eichel. By the time he was called to Frankfurt from Cracow, he was already regarded as one of the great scholars of his day. He thus enjoyed much more favourable terms of employment than his predecessor. He received a substantial income, and the community undertook to arrange for the City Council to give his married children right of residence in Frankfurt under the residence code. As a rabbi, Horowitz had to undertake to adjudicate free of charge in any disputes where sums in excess of 20 guilders were being claimed. He was allowed to dispense the honorary title of Morenu ("Our Teacher") only with the consent of the rabbinical judges or the community leadership. His principal work, on which he laboured for many years and which was the basis of his great repute, was entitled "Shnei Luchoth haBrith" (The Two Tables of the Covenant). His popular name "Shl'oh" derives from an abbreviation of this title. He was regarded as an undisputed authority in matters of both Jewish law and the mysticism of the Kabbalah. He regarded love of one's neighbour as one of the most important foundations of Judaism, and the one on which the love of God was based.
When the entire Community was driven out of the town during the Fettmilch Uprising in 1614, he left Frankfurt and went to Prague, where he was elected chief rabbi. In 1622 he emigrated to Palestine, dying eight years later in Tiberias.