During the Second World War, about 12,000 Jews were forced into the so-called Little Jewish Ghetto (Stiklių, Gaono, Antokolskio, Žydų Str.). The Little Ghetto survived until 1941.
The Great Vilnius Ghetto was created on 6 September 1941 and liquidated on 23 September 1943 (on Lydos, Rūdninkų, Mėsinių, Ašmenos, Žemaitijos, Dysnos, Šiaulių, Ligoninės streets). There were about 29,000 Jews in the Great Ghetto, most of who were killed in Paneriai. Rūdninkų g. 18 is the site of the main gate to the Great Ghetto, marked by a memorial plaque with a ghetto plan. The quarter between Ašmenos, Dysnos and Mėsinių streets is the first quarter of the restored historic Vilnius, and home to the Jewish Cultural and Information Centre. Žemaitijos Street was named after M. Strašūnas in 1921-1951.
The books collected by Matitjachas Strašūnas were the basis of the largest Judaic library in Europe (1892), which was destroyed along with the Great Synagogue. After Lithuania regained its independence, the day of the liquidation of the Great Vilnius Ghetto (23 September) was announced as the commemoration day for the victims of the genocide of the Lithuanian Jews.
Today, a kindergarten stands in the place of the Great Synagogue, adjacent to the Gaon Monument. Narrow and crooked streets with transverse arcades have retained their original appearance, and some ancient architecture has been restored: primarily houses on Stiklių and Gaono Streets.
The former Great Synagogue stood on Žydų Street and could accommodate about 5,000 believers. Next to it stood the Gaon house of prayer, the famous Strašūnas Library, and other religious buildings belonging to the synagogue. Soviet authorities destroyed them all.