Blades' father is a percussionist-turned-detective and his mother was a singer and radio performer.
After obtaining degrees in political science and law at Panama's Universidad Nacional, Blades worked at the Bank of Panama as a lawyer. In 1974, Blades moved to the United States, staying temporarily with his exiled parents in Miami before moving to New York City. Blades began his musical career in New York playing with local bands while working in the mailroom at Fania Records, and soon was working with salseros Ray Barretto and Larry Harlow. Shortly thereafter Blades started collaborating with trombonist and band leader Willie Colón, and they recorded several albums together. Their album Siembra (1978) became the best-selling salsa record in history.
After 1980, Blades tried to terminate his contract with Fania, but he was contractually obligated to record several more albums. These were generally toss-offs and Blades himself told his fans to avoid them. When he was free of his contractual obligations, Blades signed with another label, Electra, and assembled a top-notch band (known variously as Seis Del Solar or Son Del Solar) and recorded a number of albums with them.
In the early 1980s, Blades began his career in films as a composer of soundtracks. In 1983, Blades got his first acting role in The Last Fight writing the title song as well as portraying a singer-turned-boxer vying for a championship. In 1985, Blades gained widespread recognition as co-writer and star of the independent film Crossover Dreams as a New York salsa singer willing to do anything to break into the mainstream. He was also the subject of Robert Mugge's documentary The Return of Ruben Blades, which debuted at that year's Denver Film Festival. Through the 1990s he acted in films, got a doctorate in international law from Harvard University, mounted his unsuccessful presidential bid, and continued to make salsa records.
His many film appearances include The Milagro Beanfield War (1988), The Two Jakes (1990), Mo' Better Blues (1990), and Devil's Own (1997). In 1999, he played Mexican artist Diego Rivera in Tim Robbins' Cradle Will Rock In 1997, Blades headed the cast of singer/songwriter Paul Simon's first Broadway musical, The Capeman, based on a true story about a violent youth who becomes a poet in prison.
Blades' 1999 album Tiempos which he made with the 12-piece Costa Rican band Editus, represented a break from his salsa past and a rejection of commercial trends in Latin music.
Blades has stated in interviews that he believes his biggest mistake was releasing an English-language album in 1988 in the wake of his 1987 Grammy for Escenas — a trap he sees other Latin artists falling into.
Blades has had great success in the Anglophone movie world, but musically he has done well keeping close to his Latin roots.
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