Is This Desire? found Harvey switching from her earlier guitar-driven rock style into subtler, quieter, atmospheric soundscapes and mood pieces based around keyboards, bass and electronics. There were reports that Harvey gave herself so completely to the record that it was detrimental to her health. It was claimed that she was particularly unsettled by the dark, distorted missing girl narrative of "My Beautiful Leah." She told Q magazine April 2011: "I was aware that Is This Desire? was a very uncomfortable record. But there was nothing else that was sounding like it and that really excited me. I'd never explored really debasing keyboards and drum equipment and loop and samples. Really debasing my voice. And (being) debasing lyrically. Clawing things back into minimalism, very stark contrasts of light and shade. Maybe at the time it was feeling like quite a gamble for me. I'm really glad I went through with it cos it's something that I feel really proud of now."
When asked by NME if the album's cast of female characters, such as Leah, was created as a way to distance herself from the record's emotions, Harvey replied: "It's funny you should say that because I think there's more of myself in this album than there has ever been in any other. Whatever I've written all comes from inside me and my experience. Whether I write about that in another person's name or my own, there's a lot of me in there. Because I finally feel comfortable saying 'I am Polly, I am a songwriter, I'm a young woman of 28.' I'm comfortable with that for the first time in my life. I like myself. I am allowing myself to be myself for the first time ever."
Harvey, who had suffered nervous breakdowns in the past, entered another period of depression during the making of this album, which took more than a year to finish. She had just broken up with fellow alt rocker Nick Cave, who channeled his grief over the breakup into his acclaimed album The Boatman Calls. Harvey didn't realize how much she was suffering over the split, among other issues, until she played back "My Beautiful Leah." She told The Guardian: "I listened back to that song and I thought 'No! This is enough! No more of this! I don't want to be like this.' Because it was all so black and white, and life just isn't black and white. I knew I needed to get help. I wanted to get help."
Harvey changed her songwriting approach for the album. "Writing on different instruments changes the way the songs come out," she explained. "I used to write all my songs on guitar, and they come out physically different to the ones you write on keyboards - which is what I did for Is This Desire? I had one tiny keyboard, no more than a foot long, and when you're in this [hunched over] position, you tend to write more... thoughtfully."