"Little Sister" was the first single released by the rock group Queens of the Stone Age from their fourth album Lullabies to Paralyze. It was first released in December 2004 as a promotional single, but was later released as a commercial single on March 7, 2005. The song was recorded live in the studio in one take.

The song had been in the works for quite a while. An early version was recorded with Dave Grohl in 2002 for the album Songs for the Deaf, but was scrapped. The unfinished recording was later distributed on a bootleg recording compilation. According to Josh Homme, the song was inspired by the "sort of sexual twist" of Doc Pomus's song of the same name, which is probably best known as recorded by Elvis Presley: "I like the amalgam of imagery that it puts forward, that throwing a little pebble at the girl's windows late at night, you know, trying to creep in the back door, you know. And I also love the Elvis song 'Little Sister' because I like the sort of sexual twist that's put on by 'little sister don't you do what your big sister done."

When this song was performed on Saturday Night Live on May 14, 2005, actor/comedian Will Ferrell, who hosted the show, came onstage and played the cowbell as fictional Blue Öyster Cult member Gene Frenkle. This was a reprise of a role that Ferrell played in a famous 2000 sketch in which actor Christopher Walken demands, "More cowbell!" during the studio recording of that band's famous song, "(Don't Fear) The Reaper", much to the chagrin of the rest of the band. The cowbell sound is in fact made by a jam block, as seen on the music video for the song; however, since his arrival in 2013, the band's subsequent drummer Jon Theodore has used a cowbell during live performances of the song. Pearl Jam frontman Eddie Vedder has performed the song twice with the band, in 2011 at his own PJ20 festival playing the jam block and in 2013 at Lollapalooza Chile playing the cowbell, also providing backing vocals on both occasions. The song has also been featured in the show Entourage.

...
Wikipedia