Rabbi Raphael Nathan Nata Rabinovitch (Rabbinovicz) was born in 5595 (1835) in Novo-Zhagory (Žagarė), in the Kovno province of Russian Lithuania, the son of Rabbi Shlomo Zalkind, into a distinguished but poor family whose lineage was traced back to the Maharal of Prague. At about thirteen and a half he went to live in Wilkomir with Rabbi Yosef ben Yisrael Isser Padva, who fed him for two and a half years and became his principal teacher; he later married his teacher's niece and continued to consult him every year until the rabbi's death in 5621.

He continued his studies in Keidan, where he became known as "the prodigy of Keidan" and married the daughter of Rabbi Aharon ben Yisrael Isser Padva, who supported him, and then in Kapulie, near Minsk. In 5614 he moved to Eishyshok and Vilna, where he befriended the bibliographer Yitzchak Eizik Ben-Yaakov; already at sixteen he had compiled a third part of Siftei Yeshenim. In Vilna he copied in three months the manuscript of the responsa of the Maharam of Rothenburg, then left the city, apparently to avoid conscription, and settled in Lemberg, where he printed the responsa in 5620 with the approbations of Rabbi Yosef Shaul Nathanson, who used to rise when he entered the synagogue even though he was only twenty-five.

After stays in Pressburg and Vienna, where Aharon Jellinek told him about the Talmud manuscript in Munich, he reached that city and there, on 3 Elul 5623, began his life's work, Dikdukei Soferim. Supported by the banker and bibliophile Avraham Merzbacher, he collated the Munich manuscript of 1342, the only complete surviving manuscript of the Babylonian Talmud, with the first printed editions and with other manuscripts (Paris, Oxford, London, Parma), recording every variant and weighing it against the words of the Rishonim. The first volume, on Berachot, appeared in 5628 (1867); fifteen volumes were published in his lifetime and a sixteenth, on Chullin, after his death. He trusted no one else to copy manuscripts: after a cigarette burned a few lines of his work, three copyists returned three different versions of the missing text.

His introduction, Maamar al Hadpasat HaTalmud, traces the history of the printed Talmud from Soncino (5244) to Lemberg (5637) and became a foundational work of Hebrew bibliography. He also edited Gaon Yaakov on Eruvin, Yichusei Tannaim VeAmoraim and his teacher's Kuntres Ikrei HaAvodah. To support himself he had to deal in books and manuscripts.

On a business trip he contracted pneumonia in Kiev and died there on 24 Kislev 5649 (November 28, 1888), aged fifty-three, leaving a widow and an only son. The dignitaries of Kiev honored him greatly and buried him among the great of the city.