"4 Minutes" was released as the album's lead single and peaked at number three on the Billboard Hot 100. It was Madonna's 37th top-ten hit on the chart—it pushed Madonna past Elvis Presley as the artist with the most top-ten hits. In the UK she retained her record for the most number-one singles for a female artist; "4 Minutes" becoming her thirteenth. At the 23rd Japan Gold Disc Awards, Madonna received her fifth Artist of the Year trophy from Recording Industry Association of Japan, the most for any artist. To further promote the album, Madonna embarked on the Sticky & Sweet Tour; her first major venture with Live Nation. With a gross of $280 million, it became the highest-grossing tour by a solo artist then, surpassing the previous record Madonna set with the Confessions Tour; it was later surpassed by Roger Waters' The Wall Live. It was extended to the next year, adding new European dates, and after it ended, the total gross was $408 million.

Which single was released as the album's lead single?