Aims and objectives. This literature review aims to delineate the determinants of perceived burden by informal caregivers and provide insight into the interrelatedness between these determinants. Background. Despite the attention given to the various determinants of perceived burden, their interrelatedness has not been unravelled. Insight into this interrelatedness is mandatory for the development of successful, complex, multivariate interventions to reduce perceived burden of informal caregivers. Design. Systematic review. Method. Four electronic databases, CINAHL, Embase psychiatry, Medline, Psychinfo and reference lists of selected articles, were searched. Publications between January 1985-2008 were included if they concerned mental illness, burden and care giving. Articles were selected according to predefined inclusion and exclusion criteria. Results. The results of mostly descriptive, cross-sectional and univariate research and the more process-oriented results coming from qualitative burden research are organised in a process orientated conceptual scheme or model adapted from the stress-theoretical framework by Lazarus and Folkman. The model indicates that perceived burden must be understood through the individual appraisal of stressors and the availability and use of internal and external resources. Perceived burden is the outcome of multiple, clinically overlapping psychiatric problems, problematic behaviour and functional disabilities. Conclusions. So far, intervention programs to reduce perceived burden of informal caregivers have not devoted much attention to the interrelatedness of the origins of burden. The conceptual model provides an overview of the various determinants of perceived burden and a clear picture of the possible interrelatedness appears. This overview of the most important sources of burden helps to develop a complex, multivariate intervention that is comprehensive, long-term, individually tailored and has the flexibility to meet the dynamics of burden over time. Relevance to clinical practice. Use of the conceptual model is crucial to professional nursing and the quality of support of informal caregivers. © 2011 Blackwell Publishing Ltd.