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. She once again appeared as Beatrice in a critically acclaimed production of Much Ado About Nothing at Shakespeare's Globe Theatre in 2011, playing opposite Charles Edwards as Benedick and starred in the Old Vic production of The Duchess of Malfi in 2012. She made her directorial debut with a production of Macbeth at Shakespeare's Globe Theatre in 2013.
Best also co-stars as Sally Ride, the first American woman in space, alongside William Hurt in The Challenger, a British made for TV dramatization of the Rogers Commission set up to investigate the Challenger accident of 1986.