Castiglione joined the Red Sox broadcast team in 1983, After Starr's departure at the end of the 1992 season, Castiglione became the team's lead radio announcer along with
Jerry Trupiano. Castiglione became nationally known when the team won the
2004 World Series, with his broadcast of the end of the game. and
Glenn Geffner. With Geffner leaving for the
Florida Marlins broadcast booth, Castiglione shared the booth with Dave O'Brien,
Dale Arnold or
Jon Rish in 2008. Dave O'Brien and Jon Rish were his partners from 2009 through April 2013. In 2011, Dale Arnold returned to be the primary fill in on Wednesday games. Starting in May 2013, Rob Bradford,
Lou Merloni and O'Brien were his partners after John Ryder replaced Rish, with Merloni and Bradford stepping in for fill-in play by play duties. In 2011, O'Brien became the lead announcer with Castiglione moving back to the secondary announcing role. Castiglione handled play-by-play in innings 3–4 and 6–7 with O'Brien, and all innings when working with Bradford and Merloni. In 2016, with O'Brien moving to
New England Sports Network (NESN), the Red Sox television network, Castiglione began working with former
Pittsburgh Pirates broadcaster
Tim Neverett and once again was the primary game announcer calling innings 1–2, 5 and 8–9 on
WEEI. In 2017, Castiglione and Neverett rotated games as the primary and secondary announcers. On September 20, 2018, as part of a promotion called "A Rivalry in the Booth", Castiglione switched places with New York Yankees radio broadcaster
John Sterling in the fourth inning. During the
2018 American League Championship Series (ALCS), Castiglione reacted to a catch made by
Andrew Benintendi made in the ninth inning of Game 4. Castiglione fell out of his chair, and proceeded to finish the commentary with co-commentator Neverett after the incident. For the 2023 season, Castiglione began working a reduced role, only calling 81 games as the primary announcer in order to spend more time with his family. He worked with
Will Flemming and
Sean McDonough as secondary announcers, along with former player Lou Merloni. On September 15, 2024, Castiglione announced his retirement from the Red Sox' broadcast booth following the 2024 season. He stated that he would continue in an ambassador-type role for the team. Castiglione was honored by the Red Sox on September 29 with a pregame ceremony, as various players whom he covered over his 42 year stint showed up to pay their respects to his career.
Pedro Martinez joined Castiglione in the radio booth, as he recalled the longevity of his career, and NESN honored Castiglione by simulcasting his WEEI broadcast on television during the top of the ninth inning. Castiglione ended his broadcast as he traditionally did at the close of each season since 1989, reciting a passage by
Bart Giamatti from the essay "The Green Fields of the Mind". "[Baseball] breaks your heart. It is designed to break your heart. The game begins in the spring, when everything else begins again, and it blossoms in the summer, filling the afternoons and evenings, and then as soon as the chill rains come, it stops and leaves you to face the fall all alone. You count on it, rely on it to buffer the passage of time, to keep the memory of sunshine and high skies alive, and then just when the days are all twilight, when you need it most, it stops." ==Awards and honors==