International surveys have found consistently high rates of cannabis use in schizophrenia. This chapter briefly reviews potential biological, personality and cognitive mechanisms underpinning the relationship between cannabis use and psychosis. A growing number of studies have examined motives and expectancies for cannabis use among individuals with psychosis. Quantitative studies using valid and reliable measures of motives and expectancies for substance use in psychosis report similar findings. A number of biological models have focused on the role of the endogenous cannabinoid system on neurodevelopment and brain functioning via activation of the dopamine and glutaminergic systems and suppression of gamma-aminobutyric acid (GABA) functions. The relationship between cannabis and psychosis is likely to involve a complex interaction between biological, psychological and environmental variables. Research has also highlighted the potential importance of genetic and biological factors, stress, coping style, negative effect as well as cannabis-use motives and expectancies.