Current practice parameters state that extracts rich in proteases, such as fungal and insect extracts, can be combined during preparation of allergy immunotherapy vaccines. However, until recently, this guideline has not been the subject of investigation. Scientists now have data that shed light on high-protease allergenic extract mixtures used in allergy immunotherapy. A study published in Annals of Allergy, Asthma & Immunology in 2012 reports on the compatibility of combining fungal and insect extracts and emphasizes the importance of understanding how protease activities and total glycerin levels in allergy extracts can affect the stability of allergy immunotherapy vaccine mixtures. This research provides a critical assessment of the mixing compatibilities of several well-characterized high-protease extracts and may influence future immunotherapy practice parameters and immunotherapy extract preparation guidelines.