In recent years, there has been tremendous progress in elucidating the molecular bases of genodermatoses. The interface between genetics and dermatology has broadened with the identification of "new" heritable disorders, improved recognition of phenotypic spectrums, and integration of molecular and clinical data to simplify disease categorization and highlight relationships between conditions. With the advent of next-generation sequencing and other technological advances, dermatologists have promising new tools for diagnosis of genodermatoses. This article first addresses phenotypic characterization and classification with the use of online databases, considering concepts of clinical and genetic heterogeneity. Indications for genetic testing related to medical care and patient/family decision making are discussed. Standard genetic testing is reviewed, including resources for finding specialized laboratories, methods of gene analysis, and patient/family counseling. The benefits and challenges associated with multigene panels, array-based analysis (eg, copy number variation, linkage, and homozygosity), and whole-exome or whole-genome sequencing are then examined. Specific issues relating to molecular analysis of mosaic skin conditions and prenatal/preimplantation diagnosis are also presented. Use of the modern molecular diagnostics described herein enhance our ability to counsel, monitor, and treat patients and families affected by genodermatoses, with broader benefits of providing insights into cutaneous physiology and multifactorial skin disorders.