Plant diseases matter because they cause crop losses, which in turn impact on (agro)systems performances, sustainability, natural resources, societies, and even sometimes History. First comes the ‘untaken harvest’: the gap between the actually harvested yield and the yield that would be attainable in absence of disease injury. Crop loss estimates allow, on principle, to generate objective estimates of the contribution of plant diseases to food insecurity. We shall present some estimates at a global scale, bearing in mind that (1) yield loss assessment entails ground-truth that is exceedingly difficult to acquire, and (2) extrapolation hypotheses. We also care about crop loss because plant diseases do not only reduce yields, but also affect the quality of agricultural products. This is particularly the case for fungal mycotoxins, which have attracted too little attention until recently, especially in the developing world. A third element is the ‘double penalty’ associated with crop losses: each harvest unit lost to disease entails corresponding losses of energy, labor, water, and more generally, natural resources invested in the crop, thus affecting the sustainability of agrosystems. Lastly, plant disease epidemics have had documented effects on societies and History, which will be exemplified from recent literature. The quantification of crop loss to plant diseases, their analysis, and the interpretation of their consequences involve multidisciplinary insights.