In Italy, the consumption of illegal drugs became a public problem in the late 1960s. At first, the talks and policies focused on heroin use. However, in the 1990s, the drug issue in Italy focused on four substances: heroin (used mainly by adult males), ecstasy (male and female young adults), cocaine (socially integrated young adults), and marijuana (no distinct user profile). With regard to laws and policies over these four decades, a back-and-forth occurred between a socio-health focus and a quasi-prohibitionist standpoint, with the latter becoming more dominant in the last decade. Many scientific and political debates took place. Despite the arguments of experts, the laws of 1990 and 2005 clearly suggest that the prohibitionist approach was a winning path to achieving political consensus. It is not surprising that the center-left government (2006–2008) has not managed to achieve the stated objective of implementing a policy that takes the complexity of this issue into account.