Allergic diseases are the most common chronic immune-mediated disorders, and can manifest with an enormous diversity in clinical severity and symptoms. Underlying mechanisms for the adverse immune response to allergens and its downregulation by treatment are still being revealed. As a result, there have been, and still are, major challenges in diagnosis, prediction of disease progression/evolution and treatment. Currently, the only corrective treatment available is allergen immunotherapy (AIT). AIT modifies the immune response through long-term repeated exposure to defined doses of allergen. However, as the treatment usually needs to be continued for several years to be effective, and can be accompanied by adverse reactions, many patients face difficulties completing their schedule. Long-term therapy also potentially incurs high costs. Therefore, there is a great need for objective markers to predict or to monitor individual patient’s beneficial changes in immune response during therapy so that efficacy can be identified as early as possible. In this review we specifically address recent technical developments that have generated new insights into allergic disease pathogenesis, and how these could potentially be translated into routine laboratory assays for disease monitoring during AIT that are relatively inexpensive, robust and scalable.