"Hit 'Em Up" is a diss song by rap artist 2Pac featuring his group the Outlawz. It is the B-side to the single "How Do U Want It", released on June 4, 1996. The song's lyrics contain vicious insults to several East Coast rappers, chief among them, Shakur's former friend turned rival, The Notorious B.I.G., also known as Biggie Smalls.

Puffy had trouble understanding the sheer rage Shakur had expressed for Biggie in "Hit 'Em Up". He also responded by reinforcing his and Biggie's innocence regarding the shooting and went on to say that prior to the incident they "were friends", and that they "would have never done nothing to hurt him." In an interview with Vibe Magazine concerning Shakur's allegations of Biggie and Puffy having prior knowledge of the ambush, Puffy stated:  He ain't mad at the niggas that shot him; he knows where they're at. He knows who shot him. If you ask him, he knows, and everybody in the street knows, and he's not stepping to them, because he knows that he's not gonna get away with that shit. To me, that's some real sucker shit. Be mad at everybody, man; don't be using niggas as scapegoats. We know that he's a nice guy from New York. All shit aside, Tupac is a nice, good-hearted guy.  Lil' Kim responded on the original version of her song "Big Momma Thang", which was aimed at Biggie's wife, Faith Evans, and Shakur. Junior M.A.F.I.A. recorded a music video for the song "Get Money", which has been regarded as a diss to Shakur. Biggie denies these claims, stating: "It's just a video; ain't nobody got no time to make no diss on nobody." Lil' Cease said after the release that Biggie still had love for Shakur, and even respected him. The attack on Mobb Deep came as a response for their involvement on the song "L.A L.A" by Capone-N-Noreaga, which was a retaliation to Snoop Dogg and Tha Dogg Pound's song "New York, New York" music video in which members of Tha Dogg Pound and Death Row are seen knocking down buildings in New York City. Mobb Deep responded to Shakur with the track "Drop a Gem on 'em". It was first released as a promotional single, and later appeared on their album Hell on Earth. Lyrically, it did not specifically name Shakur, but it did allude to the shooting incident. It has also been noted for erroneously stating the cost of the assets Shakur had taken from him during the shooting incident. Bronx rapper King Sun also responded to Shakur with "New York Love (All Eyez On Sun)".

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