The film has been in production for many years. Originally Mandy Moore was cast as Lucy, Michelle Williams was cast as Tess and Peter Sarsgaard was cast as Campbell. Later, Steve Coogan was cast as Campbell and Amber Tamblyn was cast as Tess, Kelli Garner was cast as Peggy, Paul Dano was cast as Jim, Alison Pill was cast as Ann and the singer Nellie McKay was cast as Sue . In early 2008 all six dropped out and Amanda Seyfried was given the role of the character Peggy. She was then cast as Sophie in the film Mamma Mia! (2008) and dropped out of What Goes Up (2009) and was replaced by Sarah Lind. Hilary Duff and Olivia Thirlby were then cast in the roles of Lucy and Tess respectively.
Josh Peck, Ingrid Nilson and Andrea Brooks were then cast in the roles of Jim, Ann and Sue respectively.