A skin sensitizer induces allergic contact dermatitis upon repeated dermal exposure, often containing electrophilic components that interact with skin proteins. Skin sensitization testing is mandatory for various consumer products, and the OECD promotes in vitro approaches to address mechanistic events in this process. To streamline diverse approaches and ensure comparable information to the Local Lymph Node Assay, the OECD has released a Guideline Document on Defined Approaches for skin sensitization (OECD TG 497). This guideline aims to harmonize methods, achieve consistent information, and facilitate hazard identification and discrimination between sensitizing and non-sensitizing substances.