The song became the biggest hit of Hatfield's career, reaching number one on the US Billboard Modern Rock Tracks chart.

In an interview with Spin magazine, Hatfield stated the song came about due to her fixation on existential longing.

However, Rafferty never knew "My Sister" was partly about her until she read Hatfield's book When I Grow Up: A Memoir, released in 2008.

[2] Drummer Todd Philips first heard "My Sister" before bassist Dean Fisher joined the group.

[2] Once Fisher joined during touring for Hatfield's debut solo album Hey Babe, Philips played the song for him and he too liked it.

Philips had trouble composing the intro with his drums, but after continuously listening to a song called "We Love You Carol and Alison" from American power pop band Game Theory's album Lolita Nation, in which the band's drummer Gil Ray plays the tom-tom drums instead of the hi-hats during the verses, he copied that strategy for "My Sister."

One of the lyrics, "She's the one who would have taken me / To my first all-ages show" refers to a Del Fuegos and Violent Femmes concert that Hatfield attended with Meg Rafferty on the latter's birthday in Boston, sometime around 1982 or 1983.

During the guitar solo, the scene changes to a silvery, bright room with a tinsel-like backdrop, and the band members are dressed in blue outfits rather than black.

After this, the red room returns, with Hatfield sitting alone and singing into a microphone with its cord heading toward the camera, mimicking the music video for "Roxanne" by the Police.

The final shot of the music video features Hatfield lying motionless with her guitar on the floor of the bright room.

I was brand new and was annoyed by the whole, "There are so many girls with guitars and we are all the same" thing [in the press], so I wrote the song as a sarcastic response, a joke really.

[7] It stayed at the top spot for only one week, losing the number-one position to Blind Melon's "No Rain" on September 18.

[12] It was also featured on the official compilation album for the countdown, but when it was reissued in 2004, "I Feel You" by Depeche Mode replaced "My Sister" on the track list.

In the end, Hatfield let this incident pass without complaint, understanding that a few people may have been sour toward her sudden success.