On 14 March 2003 Safoyev was appointed the Minister of Foreign Affairs, a post he held until 4 February 2005 when he was replaced by Elyor Ganiyev.
•
In 2003, while he was the foreign minister, allegations surfaced about his possible marriage to Gulnara Karimova, the daughter of the President of Uzbekistan Islam Karimov, and President Karimov's alleged plans for his replacement by Safoyev.