Allergic reactions due to stings of Hymenoptera species, such as honeybees or yellow jackets, are well known as severe allergies with potentially fatal outcome. Much less common is that also bites of blood-sucking insects (mosquitos, horseflies, flies, bugs, lice and fleas) and arachnids (ticks) represent relevant elicitors of allergy. Although, local cutaneous hypersensitivity reactions are more common, also severe systemic reactions can occur. In the last decades the molecular knowledge of the allergen composition of hymenoptera venoms has led to considerable improvements of diagnostic and therapeutic options. Even though blood-sucking insects might be the most common elicitors of allergy overall, surprisingly little is known about their relevant allergens and possible cross-reactivities. The lack of diagnostic tools in this area results in the fact that these allergies remain underdiagnosed and -treated.