The inherited skin fragility encompasses a heterogeneous group of disorders, collectively designated as epidermolysis bullosa, characterized by recurrent mechanically induced blisters, erosions or wounds. The spectrum of clinical manifestations is broad, as well as the molecular background. Besides the skin, mucosal membranes and other organs can be affected. In real-world practice, patients with mild genetic skin fragility usually do not require medical care and often remain underdiagnosed. In contrast, the well-defined severe EB subtypes are recognized based on typical clinical features. The molecular diagnostics is usually performed in order to allow genetic counselling and prenatal diagnosis. Besides wound care and careful management of the disease complications, new experimental targeted therapies are being developed. New very rare forms of inherited skin fragility have been identified with modern sequencing methods.