Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological, and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH, and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment is essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in the future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research.