After losing in the first round of the US Open to Maria Elena Camerin, Safina made three semifinals in the fall – in Luxembourg, the Tier I Moscow and Hasselt. In Moscow, she defeated world No. 1 Maria Sharapova in the quarterfinals, her first victory over a number one player. She also played a key role in Russia's victory against France in the Fed Cup, partnering Elena Dementieva to win the doubles rubber. Speaking in 2008, Safina stated: "that was a great experience in my life [...] it also boosted my confidence because I showed I could play well even with the [French] crowd against me." Safina finished the year ranked world No. 20, by far her highest finish.
Safina started 2008 poorly, winning just 11 of her first 21 matches. Her best result in singles play during this period was a run to the quarterfinals of Miami, defeating Lindsay Davenport in the fourth round. Safina has admitted that she was considering quitting tennis during this period. Meanwhile, she won doubles titles in Gold Coast, partnering Ágnes Szávay; and in Indian Wells, partnering Elena Vesnina.