- James Spader - Alan Shore - 2004-2008 (The Practice 2003-2004) Season 1–5
- John Larroquette - Carl Sack - 2007-2008 4–5
- Christian Clemenson - Jerry Espenson - 2005-2008 (recurring season 2-3) Season 2–5
- Tara Summers - Katie Lloyd - 2007-2008 Season 4–5
- Candice Bergen - Shirley Schmidt - 2005-2008 Season 1–5
- William Shatner - Denny Crane - 2004-2008 (The Practice 2004) Season 1–5
- Rene Auberjonois - Paul Lewiston - 2004–2008 (recurring Season 4-5) Season 1–5
- Lake Bell - Sally Heep 2004–2005 (The Practice 2004; recurring Season 3; 2007) Season 1, 3
- Rhona Mitra - Tara Wilson - 2004–2005 (The Practice 2003–2004; recurring Season 2) Season 1, 2
- Monica Potter - Lori Colson - 2004–2005 (recurring Season 2) Season 1, 2
- Mark Valley - Brad Chase - 2004–2007 (recurring Season 4) Season 1–4
- Ryan Michelle Bathe - Sara Holt - 2005–2006 Season 2
- Julie Bowen - Denise Bauer - 2005–2007, 2008 (recurring Season 5) Season 2–3, 5
- Justin Mentell - Garrett Wells - 2005–2006 Season 2
- Constance Zimmer - Claire Simms - 2006–2007 Season 3
- Craig Bierko - Jeffrey Coho - 2006–2007 Season 3
- Gary Anthony Williams - Clarence Bell - 2006–2008 Season 3–4
- Saffron Burrows - Lorraine Weller - 2007–2008 Season 4
- Taraji P. Henson - Whitney Rome - 2007–2008 Season 4
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