Twenty Five is Michael's second greatest hits album, celebrating the 25th anniversary of his music career. Released in November 2006 by Sony BMG, it debuted at no.1 in the UK. The album contains songs chiefly from Michael's solo career but also from his earlier days in Wham! It comes in two formats: two CDs or a limited edition three-CD set. The 2-CD set contained 26 tracks, including four recorded with Wham! and three new songs: "An Easier Affair"; "This Is Not Real Love" (a duet with Mutya Buena, formerly of Sugababes, which peaked at No.15 in the UK Charts); and a new version of "Heal the Pain" recorded with Paul McCartney. The limited edition three-CD version contains an additional 14 lesser known tracks, including one from Wham! and one new song, "Understand".
On 23 July 2006, Michael was again accused of engaging in anonymous public sex, this time at London's Hampstead Heath. The anonymous partner was incorrectly stated to be a 58-year-old unemployed van driver. Michael stated that he cruised for anonymous sex and that this was not an issue in his relationship with partner Kenny Goss.
In February 2006, Michael was arrested for possession of Class C drugs, an incident that he described as "my own stupid fault, as usual". He was cautioned by the police and released. In 2007, he pleaded guilty to drug–impaired driving after obstructing the road at traffic lights in Cricklewood in northwest London, and was subsequently banned from driving for two years and sentenced to community service. On 19 September 2008, Michael was arrested in a public restroom in the Hampstead Heath area for possession of Class A and C drugs. He was taken to the police station and cautioned for controlled substance possession.
Michael struggled with substance abuse. He was arrested for drug-related offences in 2006, 2008, and 2010. In September 2007, on BBC Radio 4's Desert Island Discs, Michael said that his cannabis use was a problem; he wished he could smoke less of it and was constantly trying to do so. On 5 December 2009, in an interview with The Guardian, Michael explained he had cut back on cannabis and was smoking only 'seven or eight' spliffs per day instead of the 25 per day he had formerly smoked. Michael also abused sleeping pills.
In 2006, Michael performed a free concert for NHS nurses in London to thank the nurses who had cared for his late mother. He told the audience: "Thank you for everything you do — some people appreciate it. Now if we can only get the government to do the same thing." In 2007, Michael sent the £1,450,000 piano that John Lennon used to write "Imagine" around the United States on a "peace tour", displaying at places where notable acts of violence had taken place, such as Dallas' Dealey Plaza, where US President John F. Kennedy had been shot. He devoted his 2007 concert in Sofia, from his "Twenty Five Tour" to the Bulgarian nurses prosecuted in the HIV trial in Libya. On 17 June 2008, Michael said he was thrilled by California's legalisation of same-sex marriage, calling the move "way overdue".
Between 2006 and 2008, according to reports, Michael earned £48.5 million ($97 million) from the 25 Live tour alone. In July 2014, he was reported to have been a celebrity investor in a tax avoidance scheme called Liberty. According to the Sunday Times Rich List 2015 of the wealthiest British musicians, Michael was worth £105 million.