Chemical sensitization remains an important environmental and occupational health issue. A wide range of substances have been shown to possess the ability to induce skin sensitization or respiratory sensitization. As a consequence, there is a need to have appropriate methods to identify sensitizing agents. Although a considerable investment has been made in exploring opportunities to develop methods for hazard identification and characterization, there are, as yet, no validated nonanimal methods available. A state of the art of the different in vitro approaches to identify contact and respiratory capacity of chemicals is covered in this chapter.