Best Friend may refer to:
- Best Friend, someone (singular) with whom one shares the strongest possible kind of friendship(s).
- Best Friend of Charleston, an early railroad locomotive
Best Friends may refer to:
- Best Friends Animal Society, the largest animal rescue sanctuary in the United States
- Best Friends (film), a 1982 feature film, starring Goldie Hawn and Burt Reynolds
- Best Friends, a children's novel by Jacqueline Wilson
- "Best Friends," a song by Ron Sexsmith from his 2002 album Cobblestone Runway
- "Best Friends", the German title of Nappers Never Sleep (Fillmore! episode)
- Best Friends (Main Street book), part of the Main Street book series
In music:
- Best Friends, an album created by Adnan Sami
- "Best Friend", an album by Hillsong United (band)
- "Best Friend", a song by The Beat (The English Beat) from their 1980 album I Just Can't Stop It
- "Best Friend", a song by the Danish band Toy-Box from their 1999 album Fantastic
- "Best Friend", a song by 50 Cent from the 2005 Get Rich or Die Tryin' Soundtrack
- "Best Friend", a song by Brandy Norwood
- "Best Friend", a song by Harry Nilsson
- Best Fwends, a musical group from Austin, Texas
- "Best Friends", a song by Amy Winehouse
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