The Great New Wonderful weaves five stories against the backdrop of an anxious and uncertain post-9-11 New York City.
| Actor | Role |
|---|---|
 Olympia DukakisJudy Hillerman | Judy Hillerman |
 Jim GaffiganSandie | Sandie |
 Judy GreerAllison Burbage | Allison Burbage |
 Maggie GyllenhaalEmme Keeler | Emme Keeler |
 Tom McCarthyDavie Burbage | Davie Burbage |
 Sharat SaxenaSatish | Satish |
 Naseeruddin ShahAvinash aka "Avi" | Avinash aka "Avi" |
 Tony ShalhoubDr. Trabulous | Dr. Trabulous |
 Stephen ColbertPrincipal Peersall | Principal Peersall |
 Dick LatessaJerry Binder | Jerry Binder |
 Will ArnettDanny Keeler | Danny Keeler |
 Seth GilliamClayton | Clayton |
 Anita GilletteLainie | Lainie |
 Julie DretzinJulie Driscoll | Julie Driscoll |
 Edie FalcoSafarah Polsky | Safarah Polsky |
 Jim ParsonsJustin | Justin |
 Rosemarie DeWittDebbie | Debbie |
 Alexis DzienaAngie (scenes deleted) | Angie (scenes deleted) |