Charcot-Leyden crystals (CLCs) are protein crystals produced by human eosinophils, immune cells typically associated with allergy and parasitic worm (helminth) infection. These responses involve the “type 2” arm of the immune system, and CLCs are a hallmark of the more severe pathologies that can occur during type 2 inflammation, such as allergic asthma. Although described over 160 years ago, the biological relevance of CLCs to type 2 immunity has remained unknown. On page 751 of this issue, Persson et al. (1) confirm anecdotal evidence that CLCs are a key feature of severe asthma and chronic rhinosinusitis with nasal polyps. They demonstrate that the crystals, but not the soluble proteins, are powerful promoters of allergic inflammation and can be targeted with crystal-dissolving antibodies to reverse disease symptoms.