Furtado's third album, Loose, was released in June 2006. She named it after the spontaneous, creative decisions she made while creating the album. Some have labeled her a "sellout" for seemingly abandoning her folk and rock roots in favour of hip hop and R&B, while others have criticized her for attempting to "sex up" her music and appearance to sell more records. In this album, primarily produced by Timbaland, Furtado experiments with sounds from R&B, hip hop, and 1980s music. Furtado herself describes the album's sound as punk-hop, described as "modern, poppy, spooky" and as having "a mysterious, after-midnight vibe... extremely visceral". She attributed the youthful sound of the album to the presence of her two-year-old daughter. The album received generally positive reviews from critics, with some citing the "revitalising" effect of Timbaland on Furtado's music, and others calling it "slick, smart and surprising".

Loose has become the most successful album of Furtado's career so far, as it reached number one not only in Canada and the United States, but also several countries worldwide. The album produced her first number-one hit in the United States, "Promiscuous", as well as her first number-one hit in the United Kingdom, "Maneater". The single "Say It Right" eventually became Furtado's most successful song worldwide, due to its huge success in Europe and in the United States, where it became her second number-one hit. "All Good Things (Come to an End)" became her most successful song in Europe, topping single charts in numerous countries there.

On February 16, 2007, Furtado embarked on the "Get Loose Tour". She returned in March 2007 to her hometown of Victoria to perform a concert at the Save-On Foods Memorial Centre. In honour of her visit, local leaders officially proclaimed March 21, 2007, the first day of spring, as Nelly Furtado Day. After the tour, she released her first live DVD/CD named Loose the Concert. On April 1, 2007, Furtado was a performer at and host of the 2007 Juno Awards in Saskatoon, Saskatchewan. She won all five awards for which she was nominated, including Album of the Year and Single of the Year. She also appeared on stage at the Concert for Diana at Wembley Stadium in London on July 1, 2007, where she performed "Say It Right", "Maneater", and "I'm like a Bird".

In 2007, Furtado and Justin Timberlake were featured on Timbaland's single "Give It to Me", which became her third number-one single in the U.S. and second in the UK. In late 2008, Furtado collaborated with James Morrison on a song called "Broken Strings" for his album "Songs for You, Truths for Me". The single was released on December 8 and peaked at #2 on the UK Singles Chart in early January. In 2007, Furtado leaked plans to Flare regarding a song she was set to duet for Kylie Minogue's return. However, the song was not featured on her album X but Minogue says the aforementioned song "is still outstanding" and has plans to pursue it. She said "I am looking forward to getting in the studio and doing it because I know Nelly and I would have a great time together".

On December 31, 2008 El Diario La Prensa posted an article that Furtado is planning on recording songs in English and Spanish for her upcoming album and that it is "expected to launch between May and August". Furtado will be making a guest appearance on Flo Rida's new album, the track titled "Jump" was produced by Mike Caren and Oligee. It is currently unknown whether this will be released as a single or not. Furtado has also made a guest appearance on Divine Brown's Love Chronicles, co-writting and singing on the background of the song Sunglasses.

• Karaoke Revolution Presents: American Idol Encore 2 (2008) (VG) ("I'm Like A Bird")
• Wild Child (2008) (writer: "Say it Right") (performer: "Say it Right")
• "Fama ¡a bailar!" (1 episode, 2008)
       - Episode #1.86 (2008) TV episode (writer: "Lo bueno siempre tiene un final") (performer: "Lo bueno siempre tiene un final")
• Premios Principales 2007 (2007) (TV) (writer: "All Good Things (Come to an End)") (performer: "All Good Things (Come to an End)", "Fotografía", "Te busqué")
• "Gossip Girl" (1 episode, 2007)
       - Blair Waldorf Must Pie! (2007) TV episode ("Promiscuous")
• Ratico con Juanes, Un (2007) (TV) (performer: "Fotografía")
• "Supermodelo 2006" (3 episodes, 2007)
  ... aka Supermodelo 2006 (Spain: first season title)
  ... aka Supermodelo 2007 (Spain: second season title)
  ... aka Supermodelo 2008 (Spain: third season title)
       - Episode #2.8 (2007) TV episode (writer: "Say It Right") (performer: "Say It Right")
       - Episode #2.6 (2007) TV episode (writer: "Say It Right") (performer: "Say It Right")
       - Episode #2.4 (2007) TV episode (writer: "Say It Right") (performer: "Say It Right")
• "So You Think You Can Dance" (1 episode, 2007)
       - Episode #3.13 (2007) TV episode (performer: "Childhood Dreams")
• Concert for Diana (2007) (TV) (writer: "Say It Right") (performer: "Say It Right", "I'm Like a Bird (Remix)", "Maneater")
• "CSI: NY" (2 episodes, 2007)
       - A Daze of Wine and Roaches (2007) TV episode (writer: "Give It To Me") (performer: "Give It To Me")
       - Some Buried Bones (2007) TV episode (writer: "Maneater", "All Good Things (Come To An End)") (performer: "Maneater", "All Good Things (Come To An End)")
• Epic Movie (2007) (writer: "Promiscuous") (performer: "Promiscuous")
• "Shminiya, Ha-" (1 episode, 2006)
  ... aka The Eight (International: English title)
       - The Kidnapped (2006) TV episode (performer: "Maneater") ("Maneater")
• "Operación triunfo" (1 episode, 2006)
  ... aka O.T. (Spain: promotional abbreviation)
       - Episode #5.6 (2006) TV episode (performer: "Te busqué")
• John Tucker Must Die (2006) (writer: "Maneater") (performer: "Maneater")
  ... aka John Tucker doit mourir (Canada: French title)
• School of Life (2005) (TV) (performer: "Trynna Finda Way")
• "Smallville" (2 episodes, 2002-2004)
  ... aka Smallville Beginnings (USA: rerun title)
  ... aka Smallville: Superman the Early Years (UK: promotional title)
       - Delete (2004) TV episode (performer: "Try")
       - Nicodemus (2002) TV episode (performer: "I Will Make U Cry")