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In 2008, she became both Calvin Klein Jeans newest model and spokeswoman for Coach newest luxury bags.

Because her grandparents suffered from Alzheimer's disease, the book Still Alice has had an impact on her. She contacted the author, Lisa Genova, and later landed a co-starring role in the film version of the book.

She has heterochromia, a condition where the eyes have different colors: she has one blue eye and one eye that is part hazel / part blue.

She had a relationship with actor Orlando Bloom from 2002 to 2005.

In mid-2011, she began dating American director Michael Polish, whom she met earlier that year when he directed her in Big Sur. They announced their engagement in August 2012, and married on August 31, 2013. She became the stepmother to Jasper, Polish's daughter from a previous marriage, whom Bosworth said was “hands-down the greatest unexpected gift of her life”. In August 2021, she announced her separation from Polish and were legally divorced in March 2023.

In January 2022, it was reported that she was dating actor Justin Long. In April 2023, the couple announced their engagement and they married in May 2023, less than two months after getting engaged.