A number of human pathologies have a transmission pattern that does not obey Mendelian segregation rules. This type of heredity is defined as non-Mendelian and is based on mechanisms of transgenerational epigenetic inheritance. Comprehensive information on the molecular mechanisms of it is still lacking. However, recent evidence from distantly related species including Caenorhabditis elegans, Drosophila, and mouse, points towards a role for non-coding RNA molecules in such a pattern of inheritance. While it would be too hasty to conclude that RNA molecules are at work in the transgenerational non-genetic inheritance of human pathologies, a growing number of studies seem to strongly support such a speculation.