Every disease is a mirror of interactions between genes and the environment. In monogenic disorders only one mutation can lead to a specific phenotype. However the spectrum and the degree of manifestations depend on numerous factors from the environment. Ichthyosis vulgaris is caused by a mutation in the filaggrin gene. However the phenotype is much more pronounced in the winter months. In polygenic disorders such as atopic dermatitis numerous modifying genes influence the phenotype including a mutation in filaggrin. The skin is the organ of the human body which is most commonly involved in monogenic diseases. More than one third of all genetic diseases affect the integument. At the very moment more than 350 genodermatoses are identified with functional insights. The Human Genome Project was finished in 2001 with the aim that all genes can be identified for diagnostics, pharmacogenomics potential gene therapy and to understand the principle basis of diseases. The next project called ENCODE for Enzyclopedia of DNA Elements targets to identify all functional elements in the human genome sequence. MicroRNAs seem to have great importance for the regulation of genefunctions in the skin. At the moment epigenetics is at the epicentre of modern medicine. Epigenetics is the study of non-DNA sequence-related heredity. Epigenetics is an important tool to study the relationship between the genome and the environment. In the second part cases will be presented and the way of diagnosis making will be shown. It will be shown that it is very important to find clinical key features which may allow an allocation to a genetic pathway.