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It is well established that a decrease in genetic variation can lead to reduced fitness and lack of adaptability to a changing environment. Amphibians are declining on a global scale, and we present a four-point argument as to why this taxonomic group seems especially prone to such genetic processes. We elaborate on the extent of recent fragmentation of amphibian gene pools and we propose the term dissociated populations to describe the residual population structure. To put their well-documented loss of genetic diversity into context, we provide an overview of 34 studies (covering 17 amphibian species) that address a link between genetic variation and >20 different fitness traits in amphibians. Although not all results are unequivocal, clear genetic-fitness-correlations (GFCs) are documented in the majority of the published investigations. In light of the threats faced by amphibians, it is of particular concern that the negative effects of various pollutants, pathogens and increased UV-B radiation are magnified in individuals with little genetic variability. Indeed, ongoing loss of genetic variation might be an important underlying factor in global amphibian declines.