Abstract The relationship between substance misuse and psychosis is a topic that continues to provoke discussion for several reasons. In day-to-day practice, clinicians observe the aggravating effect of substances on psychotic symptoms and are frustrated by their lack of ability to motivate patients to modify their drug-using behaviour. The proportion of people who suffer with enduring psychotic illness and who misuse substances appears to be increasing year by year and is much higher than that in the general population. A review of nine studies, mostly in the USA, concluded that approximately 40–50% of schizophrenic patients have a lifetime history of substance use disorder. The effects of substance misuse upon those with pre-existing psychotic illness are known to be significant in terms of outcome. There is evidence to suggest that certain illicit substances may actually cause the emergence of schizophrenia in susceptible individuals. Why, therefore, is substance misuse so prevalent among those with psychotic illnesses and what do we know about the relationship between the two? It is important to understand the evidence underpinning our understanding of the complex relationship between substance misuse and psychotic illness. This contribution focuses on the relevance of cannabis and stimulant misuse to psychosis, and also briefly discusses opioids, alcohol and nicotine.