Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mostly affecting small-sized arteries and usually occurring in patients with an allergic background. Eosinophils seem to play a significant role in the pathogenesis of the disease and, therefore, biologics targeting interleukin 5 (IL5), a cytokine tightly linked to eosinophils, have emerged as a promising therapeutic tool. A systematic review of Medline was conducted from 2007 to 2022 to search for data regarding the use of anti-IL5 therapies in patients with EGPA. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. The efficacy and safety of mepolizumab, an anti-IL5 monoclonal antibody (mAb), was confirmed by a randomized controlled trial (RCT), although a significant proportion of patients did not respond to this treatment. Other studies showed that both doses of 100 mg and 300 mg of mepolizumab are almost equally effective in EGPA. Benralizumab, an anti-IL5 receptor mAb has preliminary promising results and an RCT is planned to be conducted. Apart from their clinical efficacy in EGPA, anti-IL5 therapies may have steroid-sparing properties. Anti-IL5 therapies seem to be effective and safe in patients with refractory/relapsing EGPA and can be used as a steroid-sparing treatment. Nevertheless, more research is needed to clarify the pathophysiology of the disease; this may potentially lead to the identification of biomarkers to pinpoint patients most likely to respond to anti-IL5-blockade.