Milian worked as an assistant state attorney for the Dade County State Attorney's Office. She was appointed to the position by Janet Reno, who was then the state attorney for the county. In 1999, Florida governor Jeb Bush appointed Milian to the Miami Circuit Court, where she served in the Criminal Division. Prior to that, she spent five years in the Miami County Court in the Domestic Violence Court, Criminal, and Civil divisions. In 2001, she replaced Jerry Sheindlin as judge of The People's Court, and became the first Hispanic judge on any English-language television court show. Milian is listed as an adjunct faculty member of the University of Miami School of Law, teaching litigation skills.

Milian is married to John Schlesinger, a former assistant United States attorney, who in 2004 was elected to the 11th Judicial Circuit Court for Miami-Dade County, Florida. This is the same position that Milian held before retiring to The People's Court. They live in Coral Gables, Florida, with their three children: Cristina (born in 1996), Alexandra (born in 1998), and Sofia (born on November 28, 2001). She travels to Stamford, Connecticut bimonthly for three days of taping of The People's Court.

She was an honorary host for National Chairman Arnold Schwarzenegger's 2003 annual celebration of the South Florida Inner-City Games. Milian was the honorary judge for Washington's 2002 Teachers Making a Difference campaign and is actively involved in supporting Southern Florida's Children's Cancer Center's Summer Camp, hosting "Camp Court" mock trials of camp counselors by the young campers. On September 20, 2006, she received the "Groundbreaking Latina of the Year" award from Catalina and the National Association of Latina Leaders.

The People's Court has featured several arbitrators, with Milian currently holding the title of the longest-presiding arbitrator over the series. By completion of the show's 28th season (2012–13), Milian had completed twelve and a half seasons presiding over the program, officially making her the longest-running judge on The People's Court. Joseph Wapner, the show's original judge, was the previous holder of this record. On September 7, 2015, the show as a whole entered its 31st season, which is Milian's 15th season presiding over the program.

Milian was portrayed by Cecily Strong in a 2017 Saturday Night Live parody of The People's Court where she presided over a case between President Donald Trump and three judges of the United States Court of Appeals for the Ninth Circuit.