AIM: Accurate prediction of which high-risk individuals will go on to develop psychosis would assist early intervention and prevention paradigms. We sought to review investigations of prospective psychosis prediction based on markers and variables examined in longitudinal familial high-risk (FHR) studies.METHODS: We performed literature searches in MedLine, PubMed and PsycINFO for articles assessing performance characteristics of predictive clinical tests in FHR studies of psychosis. Studies were included if they reported on one or more predictive variables in subjects at FHR for psychosis. We complemented this search strategy with references drawn from articles, reviews, book chapters and monographs.RESULTS: Across generations of FHR projects, predictive studies have investigated behavioural, cognitive, psychometric, clinical, neuroimaging and other markers. Recent analyses have incorporated multivariate and multi-domain approaches to risk ascertainment, with generally modest results.CONCLUSIONS: Although a broad range of risk factors has been identified, no individual marker or combination of markers can at this time enable accurate prospective prediction of emerging psychosis for individuals at FHR. We outline the complex and multi-level nature of psychotic illness, the myriad of factors influencing its development, and methodological hurdles to accurate and reliable prediction. Prospects and challenges for future generations of FHR studies are discussed in the context of early detection and intervention strategies.