Purpose of Review <p>This review aims to analyze the evidence regarding the role of the alpha-gal sensitization in other pathologies different from alpha-gal syndrome, mainly in the chronic spontaneous urticaria.</p> Recent Findings <p>The alpha-gal syndrome can present with a spectrum of clinical manifestations, with acute urticaria in the context of food ingestion in the previous hours being the most commonly reported by affected individuals. Autoimmune mechanisms have been described in the context of chronic spontaneous urticaria; nevertheless, its pathophysiology remains incompletely understood. Recently, different authors have hypothesized that alpha-gal sensitization might be one of the underlying causes of chronic spontaneous urticaria. Studies conducted to date, mostly by US and European groups, show contradictory results. Some of them report very high prevalence rates of sensitization to alpha-gal in patients with chronic urticaria, while others show even lower sensitization prevalences than in the general population.</p> Summary <p>With the current evidence, alpha-gal sensitization cannot be associated with the onset of chronic spontaneous urticaria. Further studies with larger cohorts and proper control groups are needed to accurately assess the prevalence of alpha-gal sensitization in patients with chronic spontaneous urticaria.</p>