At the end of 2005, she climbed back up the rankings and won her first title in Beijing. On 12 June 2006, she broke into the world's top 20 for the first time. At the US Open, Kirilenko was seeded 20th and reached the third round, before losing to Aravane Rezaï.
Kirilenko made her debut for Russia at the Fed Cup tournament in April 2006. In the World Group quarterfinal tie against Belgium, she lost her singles match against 2005 US Open champion Kim Clijsters, but partnering with Dinara Safina, won her doubles match against Justine Henin and Clijsters. However, Russia ended up losing, 2–3.
In 2006, Kirilenko was selected to be the face of Adidas tennis gear designed by noted British fashion designer Stella McCartney and played exclusively in it for three years. In 2009, she was replaced by Caroline Wozniacki following the US Open.