The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta-analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966–2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross-sectionals, three case–controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta-analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross-sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51–0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross-sectional studies. In a meta-analysis, calculations showed a high level of heterogeneity (I2) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross-sectional observational studies indicates the need for population-based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial-based vaccines against atopic disease in the future.