The first generation of Isley brothers was born and raised in Cincinnati, Ohio, where they were encouraged to begin a singing career by their father, himself a professional vocalist, and their mother, a church pianist who provided musical accompaniment at their early performances. Initially a Gospel quartet, the group was comprised of Ronald, Rudolph, O'Kelly and Vernon Isley, who, as teenagers, enjoyed a local following. Vernon was killed in a 1955 bicycling accident and tenor Ronald was tapped as the remaining trio's lead vocalist. In 1957 the brothers moved to New York City where they struggled to gain recognition as a Doo-Wop act. They finally landed a record deal with RCA Records in 1959 and recorded a string of failed singles.

While performing a spirited rendition of the song "Lonely Teardrops" in Washington, D.C. two years later, they interjected the line 'You know you make me want to shout', which inspired frenzied audience feedback. An RCA executive in the audience saw the concert, and when he signed The Isleys soon after, he instructed that their first single be constructed around their crowd-pleasing catch-phrase. That first record, "Shout", was slow to take off, but it did eventually reach #47 on the Billboard Hot 100 and has since become a frequently-covered classic. Despite their initial success, The Isley Brothers failed to chart another single until 1962 when their recording of "Twist and Shout" (originally by The Topnotes) reached #17, but their version got most of its attention after The Beatles covered it. Other acts also had great success with songs that were first recorded by The Isley Brothers, such as The Outsiders, ("Respectable"), The Human Beinz ("Nobody But Me"), and Lulu ("Shout").

During the next few years the group struggled for another hit, touring constantly while their singles missed the charts. During a 1964 tour they recruited a young guitarist named Jimmy James to play in their backing band. James, who later shot to fame as Jimi Hendrix, made his first recordings with The Isleys, including the single "Testify," issued on the brothers' own T-Neck label. The following year the trio signed with Tamla, a subsidiary of Motown, where they joined forces with the famed Holland-Dozier-Holland writing and production team. Here, they scored their biggest hit yet with "This Old Heart of Mine," a Top 20 smash that peaked at #12. "This Old Heart of Mine" was their only hit on Motown however, and because the song hit number three in Britain in 1967, The Isleys relocated to England in order to sustain their flagging career. After years of writing their own material, they felt confined by the Motown assembly-line production formula, and by the time they returned stateside in 1969, they had left Tamla to resuscitate the T-Neck label.

Their next release, the muscular and funky "It's Your Thing", hit #2 on the Hot 100 chart in early 1969, and became their most successful record, earning them a Grammy Award. That year, The Isleys also welcomed a number of new members, as younger brothers Ernie and Marvin, brother-in-law Chris Jasper and family friend Everett Collins became the trio's new backing unit. Spearheaded by Ernie's hard-edged guitar leads, the group began incorporating more and more Rock material into its repertoire as the 1970s dawned, and scored hits with covers of Stephen Stills' "Love The One You're With" (#18 in 1971), Eric Burdon & War's "Spill the Wine" and Bob Dylan's "Lay Lady Lay".

In 1973, The Isleys scored a massive hit with their Rock-Funk fusion cover of their own earlier single "That Lady" (#6), follwed by "Fight The Power" (#4 in 1975). As the decade wore on, the group again altered its sound to fit into the booming Disco market. While their success on Pop radio ran dry, they frequently topped the R&B charts with singles like 1977's "The Pride", 1978's "Take Me To The Next Phase", 1979's "I Wanna Be With You" and 1980's "Don't Say Goodnight". The Isley hit machine ground to a halt in the 1980s when line-up changes tore the group apart. In 1984, Ernie and Marvin, along with Chris Jasper, defected to form their own group, Isley, Jasper, Isley, who found success a year later when they topped the R&B charts with "Caravan of Love."

On March 31, 1986, O'Kelly Isley died of a heart attack. When Rudolph Isley retired from music to become a minister in the late 1980s, it appeared that the Isley Brothers were finished. However, in 1990, The Isleys re-formed with a new line-up that featured Ronald, Marvin and Ernie Isley and scored a #10 Billboard Hot 100 smash with "This Old Heart Of Mine" that featured Rod Stewart. Although the individual members continued with solo work and side projects, The Isley Brothers forged on in one form or another throughout the decade. In 1996 they released the album "Mission to Please", produced by modern-day luminaries Babyface, Keith Sweat and R. Kelly. They reached the Top Ten again with "Down Low (Nobody Has To Know)", which made it to #4. In 1997, after charting again with the #35 hit, "Smokin' Me Out", the band announced an official hiatus.

Ronald and Ernie Isley released a new album in 2001, fittingly called "Eternal", which yielded their Billboard Pop chart #19 hit, "Contagious". The disc debuted at #3 on the Billboard R&B album charts, marking it their first commercial success of the new millennium. September 2006 brought some tough times for Ronald Isley when he was sentenced to thirty-seven months in prison for tax evasion. The 65-year-old singer was also ordered to pay $3.1 million in back taxes to the Internal Revenue Service. Isley was convicted in 2005 of five counts of tax evasion and one count of willful failure to file a tax return. Another blow was deal to the Isleys on June 6th, 2010, when bassist Marvin Isley passed away from complications of diabetes at the age of 56. The group, consisting of just Ronald and Ernie, continued to perform together on the road.