Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence on the efficacy of pharmacotherapy treatment for known HDM-allergic patients is weaker. The standard diagnostic techniques—skin prick test and specific IgE testing—can be confounded by cross-reactivity. However, component-resolved diagnosis using purified and recombinant allergens can improve the accuracy of specific IgE testing, but availability is limited. Treatment options for HDM allergy are limited and include HDM avoidance, which is widely recommended as a strategy, although evidence for its efficacy is variable. Clinical efficacy of pharmacotherapy is well documented; however, symptom relief does not extend beyond the end of treatment. Finally, allergen immunotherapy has a poor but improving evidence base (notably on sublingual tablets) and its benefits last after treatment ends. This review identifies needs for deeper physician knowledge on the extent and impact of HDM allergy in respiratory disease, as well as further development and improved access to molecular allergy diagnosis. Furthermore, there is a need for the development of better-designed clinical trials to explore the utility of allergen-specific approaches, and uptake of data into guidance for physicians on more effective diagnosis and therapy of HDM respiratory allergy in practice.