Ramis was born on November 21, 1944, in Chicago, Illinois, the son of Ruth (nee Cokee) and Nathan Ramis, who owned the Ace Food & Liquor Mart on the city's far North Side. Ramis had a Jewish upbringing. In his adult life, he did not practice any religion. He graduated from Stephen K. Hayt Elementary School in June 1958 and Nicholas Senn High School in 1962, both Chicago public schools, and in 1966 from Washington University in St. Louis, Missouri, where he was a member of the Alpha Xi chapter of Zeta Beta Tau fraternity.

In May 2010, Ramis contracted an infection that resulted in complications from autoimmune inflammatory vasculitis and lost the ability to walk. After relearning to walk he suffered a relapse of the disease in late 2011.  He died of complications of the disease on February 24, 2014 at his home on Chicago's North Shore, at age 69. A private funeral was held for him two days later with family, friends, and several collaborators in attendance including Dan Aykroyd, Chevy Chase, Eugene Levy, Dave Thomas, David Pasquesi, Andrew Alexander, and the widows of John Belushi and Bernard Sahlins. He is buried at Shalom Memorial Park in Arlington Heights.  Upon Ramis' death, President Barack Obama released a statement, saying: "when we watched his movies--from Animal House and Caddyshack to Ghostbusters and Groundhog Day--we didn't just laugh until it hurt. We questioned authority. We identified with the outsider. We rooted for the underdog. And through it all, we never lost our faith in happy endings." He ended his statement by saying he hoped Ramis "received total consciousness", in reference to a line from Caddyshack.  Ramis and longtime collaborator Bill Murray had a falling out during the filming of Groundhog Day. Shortly before Ramis' death Murray visited him, and the two spoke for the first time in 21 years. Murray gave tribute to Ramis at the 86th Academy Awards.  Ramis was paid tribute by Stephen Colbert on an episode of his show The Colbert Report. Colbert said that "as a young, bookish man with glasses looking for a role model, I might have picked Harold Ramis". He ended the show by thanking Ramis.

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