There are clear differences in individual susceptibility to the development of contact allergies; some individuals readily become allergic to many chemicals, and others remain clinically tolerant of everything that they come into contact with. A great number of molecules and pathways can contribute to the perturbation by xenobiotics and the subsequent possible immune response. It is necessary to consider susceptibility in two ways: as allergen-specific and as non-allergen-specific. It is likely that different receptor pathways and processes will be involved in the different forms of susceptibility. As investigations of the genetic control of such susceptibility have failed to identify major genetic control, it is likely that small contributions will be made by many components. Whereas genome-wide associations and transcriptome analyses may reveal genetic clues in the future, explanation of how/why the expression of multiple molecular components can be controlled in a coordinated fashion may follow from investigation of microRNAs. It is becoming clear that microRNAs can regulate the expression of multiple genes and even multiple components of biochemical pathways.