Molecular genetics is the study of the structure of genes at molecular level, and the impact of gene expression and regulation on the biology of the organism. The interplay between these two fields, genetics and biology, is a burgeoning area in all disease. In recent years the process of disease gene identification and clinical genetic diagnostic reporting has been revolutionized by the technologies discussed in this chapter, most prominently next-generation sequencing (NGS). These techniques have increased the speed and volume of genetic data generation, and have made the transition from the research sphere to the diagnostic laboratories. The identification of disease-causing genetic mutations in both inherited and sporadic paediatric dermatological conditions has begun to influence clinical management, allowing preimplantation genetic diagnosis, stratification for targeted personalized medical therapies, or gene therapy in some cases. This chapter reviews the essential terminology, key techniques and important advances needed to update paediatric dermatologists in this field, forming a basis for the detailed disease-specific chapters that follow.