Beginning in 1916 Harmonia axyridis, an orange/red lady beetle with variable black spotting, was imported into the United States from Asia. This agricultural pest-control predator established independent feral populations in North America by 1988. Subsequently, Harmonia axyridis has become a pest to homeowners and various horticultural enterprises. Seeking winter hibernation sites, ladybug swarms invade human homes/habitats primarily in the fall. With increased Harmonia axyridis exposures, human ladybug allergy was first reported in 1998. Ladybug-specific IgE hypersensitivity has been reported in all ages (1-78 years old) and both sexes. Clinical ladybug allergy manifests variously as rhinoconjunctivitis, asthma, urticaria, and angioedema. A majority, but not all, allergic individuals are primarily exposed at home. Large fall swarms and smaller spring dispersions produce corresponding peaks in ladybug allergy. Ladybug hemolymph is a primary source of allergen. Har a 1 and Har a 2 major ladybug allergens have been characterized. Ladybug allergy prevalence in one endemic area was reported as 10%. Self-report of ladybug pests at home did not predict ladybug allergy, suggesting other exposures are important also. Some individuals have no history of atopy before manifestation of ladybug allergy. Ladybug, cat, cockroach, and house-dust mites are the most likely allergens to present as isolated single positive skin tests in an allergist's office. Ladybug should be a standard skin test allergen for all allergy patients tested in endemic areas. Avoidance of ladybug exposure is paramount to treatment.