Part new wave and part new-millennium post-punk, this Las Vegas foursome originally got together in 2002. Flowers had left behind his former synth pop band, Blush Response, when he noticed a classified ad in the local newspaper placed by Keuning. Both of them were huge Oasis fans, and within weeks the two composed their soon-to-be cult hit, "Mr. Brightside." Stoermer, a former medical courier, and Vannucci, a classical percussion major at UNLV, soon joined the fray that became The Killers.

The London-based indie imprint Lizard King Records caught wind of the band's brewing hype and quickly signed them to issue a limited-edition single for "Mr. Brightside" in fall of 2003. In October, The Killers' buzz earned them a prime spot at the annual CMJ Music Marathon. A worldwide deal with Island Records followed shortly thereafter, positioning The Killers to join the ranks of Interpol, the Rapture, and the Strokes.

Shared U.K. tour dates with British Sea Power and stellastarr* in summer 2004 also gave the band the opportunity to showcase material from its debut album. Hot Fuss arrived in June and two months later, it was announced that the Killers were among the ten finalists up for the 2004 Shortlist Music Prize. Singles such as "Somebody Told Me," "Mr. Brightside," "Smile Like You Mean It," and "All These Things That I've Done" became worldwide chart hits for the group while Hot Fuss eventually earned five Grammy nominations in 2005 and sold over five million copies.

The Killers ultimately scrapped their plans of taking a break to recover from their relentless touring regime, and instead got right to work on their second album. Writing came together quickly around a common theme of longing for the way things used to be since the demise of old-fashioned American values. Soon the guys were ready to hit the studio and became the first band to record inside the newly built facility at Vegas' Palms Hotel and Casino; helming the controls were legendary producers Flood and Alan Moulder (who had previously worked together with U2 and the Smashing Pumpkins). High praise from press and fans over early music, including the Bruce Springsteen-inspired lead single "When You Were Young," led up to the highly anticipated release of Sam's Town in early October 2006.

Vocalist Brandon Flowers said that Sam's Town would be "one of the best albums people would remember 20 years from now", though the album received a mixed response from critics and fans. However, the album sold over 706,000 copies worldwide in the first week of release, with a number two debut on the Billboard chart. In the year following the release of Sam’s Town the group released a compilation album containing B-sides, rarities, and some new material. The album entitled Sawdust, released in November 2007, has been classified as Platinum by the British Phonographic Industry (BPI).

The Killers third studio album, Day & Age, was released in November 2008. The album eschewed the Americana tangents of Sam's Town in favor of pop pastiches and sleek, oddball dance-rock. The first single "Human", which had originally been planned for Sawdust, helped the band continue their commercial streak. Day & Age reached number one on the UK and Irish charts, and number six on the Billboard 200 album chart.

During the summer of 2009 The Killers headlined a number of festivals across Europe including the Friday night show of 2009's Hard Rock Calling in Hyde Park, London. They also headlined American festivals Lollapalooza and Coachella for the first time. In July The Killers recorded their first live DVD, at the Royal Albert Hall in London, which was released in November.

In January 2010 the band announced that they would be taking a short break after being on the road for the better part of six years. In late February, The Sun published the story that Flowers' mother had died after a two year fight with brain cancer. This resulted in a premature closing of their Day & Age tour cancelling the Asian dates, although they still continued with some Australian concerts. Despite their hiatus the band, invited by US President Barack Obama, played on the White House South Lawn on July 4, 2010 for the second annual "Salute To The Military".