Seafood allergies have been increasing their presence in the last 2 decades. Allergic reactions to seafood can range from mild urticarial and oral allergy syndrome to life-threatening anaphylactic reactions. Ingestion of seafood infested with Anisakis larvae can cause a disease known as anisakiasis with symptoms similar to true seafood allergy. Furthermore, some adverse reactions to seafood including histamine fish poisoning (HFP), and intolerance to histamine can trigger clinical symptoms, which, although nonallergic in origin, are similar to true immunoglobulin E (IgE)-mediated allergic reactions. Because seafood allergy usually remains a lifelong food allergy, this review focuses on the current knowledge on fish and shellfish allergens and emphasizes the importance of differentiating seafood allergy from other allergy-like reactions (anisakiasis, HFP, and intolerance to histamine). Key teaching points: • Fish and shellfish are potent allergens that can provoke serious IgE antibody-mediated adverse reactions in sensitive individuals. • Sensitization to seafood allergens can be achieved by ingestion, inhalation, or skin contact. • Shellfish major allergen, tropomyosin, shares significant homology to arthropods (dust mites and cockroaches). • Accidental exposures to seafood products cross-contaminated with fish or shellfish allergens (hidden allergens) during processing may present a health risk for sensitive individuals. • Allergens of fish parasite A. simplex present common hidden allergens in seafood, particularly in raw and undercooked home-made fish dishes. • Symptoms caused by HFP, histamine intolerance, and anisakiasis are similar to true seafood allergy.