"Shake the Disease" is Depeche Mode's thirteenth UK single recorded at Hansa Mischraum in Berlin (released on 29 April 1985), and was one of two new songs released on the compilations The Singles 81→85 (UK) / Catching Up with Depeche Mode (US) the same year, along with subsequent single "It's Called a Heart".

Band member Alan Wilder felt this song captured the essence of the band, saying that "there's a certain edge to what we do that can make people think twice about things. If we've got a choice between calling a song 'Understand Me' or 'Shake the Disease', we'll call it 'Shake the Disease'. There's a lot of perversity and innuendo in our lyrics, but nothing direct."

The lyric "I've got things to do, and I've said before that I know that you have too" is possibly a reference to the song "Stories Of Old" on the 1984 Depeche Mode album Some Great Reward, which contains the lyric "I've got things to do/You have too/And I've got to be me, you've got to be you."

The music video is the first Depeche Mode video directed by Peter Care and features an innovative camera trick to make it appear as though the band members are falling. It was shot in the town of Hounslow in London.

The track reached the top 40 on the US Billboard Hot Dance Club Play chart in November 1985. It reached number 18 in the UK singles chart. The single reached the Top 10 in Germany, Sweden, Switzerland, etc.; the song also entered the Irish Top 10 and even reached the #1 spot in Poland, where the band was very popular at that time. In France, Shake the Disease peaked at #13, remaining in the Top 50 for five and a half months.Los Angeles modern rock radio station KROQ-FM named "Shake the Disease" as the number one song of 1985.

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