TV Guide called him "the most inventive network reporter in television", and New York Magazine wrote that he's "the man who simplifies without being simple."

[5] In 1999, he hosted an eight-part prime-time series for ABC Nightline called Brave New World (which frequently featured his friends, They Might Be Giants, as musical guests).

The show often tackled science stories considered too complex for television, sometimes using cartoons and musical production numbers to illustrate abstract concepts.

In 2005, Krulwich re-established a relationship with NPR, where he made regular contributions to several programs on science topics, while continuing to produce occasional segments for ABC News.

Krulwich substitutes for the hosts of NPR's magazine shows, and from mid-2004 to January 2020 he co-hosted the Radiolab program with Jad Abumrad.

Krulwich has a prominent role in the 2021 feature documentary film Objects[6][7] as a proponent of recognizing the importance of seemingly useless keepsakes for their history and personal meaning.

[10] Krulwich said he planned to use his retirement to work on collaborations including a documentary about Oliver Sacks with Ric Burns and a project about photographer Anand Varma's cultivation of jellyfish.

The couple was featured in Act 2 of Episode 226 ("Reruns") of the Chicago Public Radio program This American Life, recounting their separate (and divergent) accounts of an event in their lives.