Persons with severe and persistent mental illnesses, e.g. schizophrenia spectrum disorders and bipolar disorder, smoke at a much higher rate than the general population. Treatment options for schizophrenia spectrum disorders and bipolar disorder often include the first-generation (typical) and second-generation (atypical) antipsychotics, which have been shown to be effective in treating both psychotic and mood symptoms. This article reviews studies examining the relationship between antipsychotic medication and cigarette smoking. These studies suggest that in persons with schizophrenia and schizoaffective disorder, typical antipsychotics may increase basal smoking and decrease people's ability to stop smoking, whereas atypical antipsychotics decrease basal smoking and promote smoking cessation. However, we found that the data available were generally of moderate quality and from small studies, and that there were conflicting findings. The review also critically assesses a number of potential mechanisms for this effect: the use of smoking as a form of self-medication for the side effects of antipsychotics, the effect of antipsychotics on smoking-related cues and the effect of antipsychotics on the appreciation of the economic cost of smoking behaviour. Gaps in the research are noted and recommendations for further study are included. More study of this important issue is needed to clarify the effect of antipsychotics on smoking behaviours.