Fratello was head coach of the Memphis Grizzlies from December 2004 to December 2006. In his first season he inherited a 5–11 team that he turned around to win 40 games and advance to the playoffs. Fratello built on that record the following year to win 49 games and return to the playoffs for a second consecutive season. Before departing in December 2006, his record was 6–24 taking his overall record with Memphis to 95–83.
Prior to working with the Grizzlies, Fratello had coached the Cleveland Cavaliers and the Atlanta Hawks. In his six seasons with the Cleveland Cavaliers his record was 248 wins and 212 losses. Fratello took the Cavaliers to the playoffs four times. Fratello coached the Hawks for seven seasons and posted a 324–250 record, making the post-season playoffs five times and winning the Central Division in 1987 with 57 wins. Fratello was named Coach of the Year for the 1985–86 NBA season. His NBA career stats are 667 wins and 548 losses for a .549 average. His teams have qualified for the playoffs in eleven of his 16 seasons as a head coach.
One of the most respected basketball minds despite having never won an NBA championship as a head coach, Fratello ranks 19th on the NBA's all-time win list and 21st in games coached.
On February 24, 2011, Fratello was officially announced as the Ukraine national basketball team head coach and on March 3, 2011, he was introduced to the Ukrainian media at a press-conference in Kyiv. After the successes he provided for Ukraine, including their first ever FIBA World Cup appearance, it was announced that Fratello would not coach for Ukraine for EuroBasket 2015. He would be replaced by Yevgin Murzin as the nation's Team Ukraine basketball team.
Fratello has been a television commentator for NBC Sports and is currently a main color commentator of TNT, working once again with longtime play-by-play announcer Marv Albert, who first paired up with Fratello in the 1990–91 NBA season as the main announcing team for the NBA on NBC. Starting with the 2008–09 NBA season Fratello also began working with Marv Albert doing New Jersey Nets games on the YES Network.
For the 2007–08 season, TNT rehired Fratello as a full-time commentator, allowing him to work once again with longtime play-by-play announcer Marv Albert, who first paired up with Fratello in the 1990–91 season as the main announcing team for the NBA on NBC. Reggie Miller, who had split time between TNT's studio and the booth the past two years, also became a full-time game analyst, joining Albert and Fratello on the sidelines.
Prior to Kerr's departure in the summer of 2014 to become the head coach of the Golden State Warriors, he was part of a 3-man booth with his YES counterpart Marv Albert and Steve Kerr.