Understanding the pathogenesis and working mechanisms of occupational asthma (OA) is crucial towards optimizing prevention and management of the disease. The study of the sensitizing and asthma-inducing properties of low-molecular-weight (LMW) agents is evolving quickly. So far, experimental research has shown that OA caused by sensitization to LMW agents does not completely fit the pathways of the traditional allergic model, in which there is a central role for immunoglobulin E. Furthermore, recent evidence indicates that chemical respiratory allergens may induce respiratory tract sensitization by routes different than inhalation, such as dermal exposure. Knowledge on OA induced by LMW is increasing, but the pathogenesis remains largely vague. Dendritic cells, T cells, eosinophils, and several cytokines and chemokines are likely involved as in atopic asthma, but through subtle differences in T cell subpopulations, cytokine balances and effector cells involved chemical-induced OA may well depend on processes that might differ substantially from those of atopic asthma. Furthermore, the involvement of the transient receptor potential channels in chemical-induced OA and irritant-induced asthma is intriguing. Further research in both humans and animals remains necessary to clarify the process of sensitization by LMW allergens and the mode of action inducing the occupational asthma phenotype. ; status: published