She is best known for having been Lancome's long-time spokesmodel and for taking roles in quirky films like ex-lover David Lynch's Blue Velvet (1986) and Wild at Heart (1990), Abel Ferrara's The Funeral (1996), and Stanley Tucci's Big Night (1996) and The Imposters (1998). She has also been in movies such as Immortal Beloved (1994) with ex-lover Gary Oldman and Death Becomes Her (1992), and done TV appearances for "Friends," "Chicago Hope" and "Merlin."

Isabella Rossellini has been married and divorced twice (once to director Martin Scorcese and once to former model Jonathan Wiedemann). She has two children, Elettra-Ingrid Wiedemann and Roberto Rossellini (adopted), and has one twin sister, Ingrid Aborne, one half-sister, Pia Lindstrom, and one brother Roberto Ingmar Rossellini.