This contribution will explore UK-based research developments in substance misuse and mental illness over the last 20 years. The main body of work revolves around research largely, but not only, funded by the Department of Health from the late 1990s. Early research revolved around alcohol, especially alcoholic hallucinosis: the relationship with schizophrenia-like illness was examined and the conclusion at that time on the basis of twin, family and clinical studies, was that very few cases did develop into schizophrenia. More recently, large general population epidemiological, and medium or small scale clinical studies, have been undertaken on the relationship between substance misuse (sometime specifically on cannabis) and the later development of mental illness especially psychosis. The presentation will aim to draw parallels with the current debate around the link between cannabis and psychosis and urges caution in too rapid an assertion that cannabis is necessarily ‘causal’ and the clinical and policy implications of the misinterpretation of evidence. A proposal will be put forward that the genesis of psychotic illness in alcohol misuse is revisited using more sophisticated research methodologies. Given the changing landscape of substance use in the UK, particularly the fashion of polysubstance use and the recognition that this may be associated with psychotic illness, other drugs that are associated with psychotic illness should be similarly investigated to determine whether there is a common mechanism that might throw light on understanding the relationship between substance use and psychotic illness or schizophrenia.