In 1976, he took over as host of his friend Avi Nelson's radio show on WHDH, in the midst of the city's unrest over forced busing and desegregation in schools.

The top-rated talk radio host in New England, he appeared in a regular weekday evening slot until his retirement.

At the end of his career, Brudnoy was, according to WBZ Radio's promotional materials, derived from Arbitron ratings, among the most-listened-to evening talk hosts in the United States.

[11] Over the years, Brudnoy also appeared as a news commentator and host on local TV stations besides WGBH, including WCVB-TV (ABC), WNAC-TV, and WBZ-TV (CBS).

After his bout with AIDS, Brudnoy began broadcasting from his apartment four nights out of five, welcoming his radio guests into his home and eagerly offering them cocktails.

[citation needed] His non-partisan, thoughtful way of discussing issues helped him gain a large following despite being based in a staunchly Democratic region.

"He couldn't care less about your party label, as long as you knew what you were talking about, because he always did"; and conservatives like then-Governor Mitt Romney who said that Brudnoy was "... a friend to hundreds of thousands of people, most of whom he never even saw in person .

It's an inheritance rich in tolerance, in faith, in the greatness of humanity, in respect for all people..."[22] In 2000, Brudnoy declared himself a member of the Libertarian Party.

"[24] But while he was a skeptic about the tenets of organized religion, during his late-2004 bout of serious illness he admitted he had prayed in various ways,[25] including with a Catholic priest who was a friend of his; and he said that he had discussed religion with several of his Jewish friends, including political commentator Jon Keller and conservative newspaper columnist Jeff Jacoby.

Brudnoy did not attempt to mask his sexuality during his adult life, but also made no direct indications of it; it was well known among his colleagues in broadcasting long before he spoke publicly about it.

His closest and oldest friend was psychologist Dr. Ward Cromer, with whom he took dozens of trips abroad, and who was incorrectly assumed by many to be Brudnoy's sexual partner.

It was at that time, in order to conserve his strength, that he broadcast his show from his apartment in the Back Bay section of Boston during part of 1994.

After hospitalization and treatment, including another period of being considered near death, the cancer went into apparent remission, and Brudnoy returned to work, with a strained voice, in March 2004.

On December 8, Brudnoy made his last radio broadcast on his show via a deathbed interview with WBZ reporter Gary LaPierre.

[30] The following day, Brudnoy ordered his doctors to remove all artificial life support systems, leaving him only with oxygen, morphine, and minimal food.

A public memorial was held for Brudnoy on February 27, 2005, at the Cutler Majestic Theater in Boston, arranged by his WBZ colleagues and Emerson College (which had previously awarded him an honorary doctorate).

The memorial service included the participation of the brothers of the Phi Alpha Tau fraternity of Emerson College whom Brudnoy had mentored.