OBJECTIVE This was to review and assess the studies on aetiology of Molar-Incisor Hypomineralisation (MIH) or, as a proxy, of demarcated opacities in permanent first molars and to consider the potential factors involved with findings obtained in animal experiments. METHODS A systematic search by Medline online database was performed. Abstracts behind appropriate titles were studied and finally the full articles were evaluated for their strength of evidence in the aetiology of MIH. RESULTS From a total of 1,142 articles 28 were identified and selected for review. The selected papers covered medical problems in prenatal, perinatal and postnatal period, medication of the child during the first years of life, and exposure to fluoride or environmental toxicants (dioxins and PCBs) in the early childhood. Based on the assessment of the articles it was still not possible to specifically name those factors causing MIH although correlations between several potential factors and MIH were presented. Among the factors suggested and found to cause enamel defects in animal experiments were: high fever, hypoxia, hypocalcaemia, exposure to antibiotics (amoxicillin, a macrolide), and dioxins. CONCLUSIONS Despite increased knowledge on the aetiology of MIH insufficient evidence to verify the causative factors exists. Further studies, especially prospective ones, are needed to improve the level and strength of evidence of the role of the present putative factors and to reveal new factors that may be involved. Any combined effect of several factors should be taken into account. Experimental dose/response studies and research on the molecular mechanisms causing the abnormal function of the ameloblasts are also necessary to deepen our knowledge of MIH.