For over a century, multinodular goitre (MNG) has been looked upon as the simple consequence of iodine deficiency. This view is now no longer tenable. Indeed, many characteristics of MNG do not fit with the iodine deficiency concept. For example, nodular goitre is a frequent disease even in those countries where the population is never exposed to iodine shortage. Moreover, neither multinodularity, nor the proverbial heterogeneity of growth and function or the autonomous, thyroid stimulating hormone (TSH)-independent growth of many goitres are compatible with the iodine deficiency concept, let alone subclinical or overt thyrotoxicosis which often complicates the course of a MNG. Recent investigations have led to the conclusion that MNGs are true benign neoplasias that are due to the high intrinsic growth potential of a variable, genetically predetermined fraction of all thyrocytes. Gross and heritable metabolic and functional differences between the individual thyrocytes, from which new follicles are generated during goitrogenesis, are the cause of the often spectacular functional and structural heterogeneity of MNG. Superimposed iodine deficiency changes the epidemiology, but not the basic mechanisms of goitrogenesis. These new pathogenetic concepts have a profound impact on the clinical management of MNG.