Won an Olivier Award for playing the title role in Hedda Gabler and was nominated for the same award the following year for her performance as Josie in Eugene O'Neill's play A Moon For The Misbegotten at the Old Vic Theatre in London.
In early 2007, she starred in a Sheffield Crucible production of As You Like It which played for a short time at the RSC's Swan Theatre in Stratford as part of their Complete Works season. In the same year she performed in the Broadway transfer of A Moon For The Misbegotten for which she was nominated for a Tony Award as Best Actress in a Play.
Best appeared in Harold Pinter's The Homecoming at the Cort Theatre in New York, which co-starred Ian McShane, Raúl Esparza and Michael McKean. Daniel Sullivan directed the 20-week limited engagement, which ran until 13 April 2008.
Television appearances include Prime Suspect: The Final Act (2006), Waking the Dead (2004), Shackleton (2002), and The Inspector Lynley Mysteries (2005).
She appears as Lucrece in the Naxos audiobook version of Shakespeare's The Rape of Lucrece. She also starred in a 2000 BBC Radio 4 production of Emma.
Best co-stars as Dr. Eleanor O'Hara in the Showtime dark comedy series Nurse Jackie, that premiered in June 2009. She played the Duchess of Windsor — Wallis Simpson — in The King's Speech, starring Colin Firth and Geoffrey Rush