The top podcast on iTunes in recent days is This American Life. A repeat of the award winning radio show that you can download to listen to at your convenience.
Almost everyone has heard This American Life, somewhere, sometime. It’s awesome.
This American Life (TAL) is a weekly hour-long radio program produced by Chicago Public Radio. It is distributed by Public Radio International and is also available as a free weekly podcast. TAL, hosted by Ira Glass (cousin of composer Phillip Glass), is primarily a journalistic non-fiction program, although it has also featured essays, memoirs, field recordings, short fiction, and found footage.
A television program sharing the name and basic structure of the radio program airs on the Showtime cable network, and features Ira Glass as the host and executive producer. The first episode aired on March 22, 2007.
Similar, but even better, and far less well known, is WNYC’s Radio Lab. They have far fewer episodes too. Radio Lab is the future of audio entertainment, I think. Very innovative.

To check out these podcasts, listen on their home pages:
Or, far easier, search for them in the iTunes store if you use that software. (Surprisingly, the Zune store just added “podcasts”, as well.)
