Parietaria pollen is the most important cause of pollen allergies in the Mediterranean area, as Parietaria is widespread in this region. Many issues are associated with Parietaria allergy, including the duration of the pollen season (many doctors in fact believe that it lasts throughout the year), pollen load (which seems to be increasing over time), the impact of age (on IgE production and symptom severity), inflammatory changes (after pollen exposure), and the choice of allergen immunotherapy (AIT). In addition, molecular diagnostics allows for the defining of a correct diagnosis, differentiating between mere sensitization and true allergy. This review considers these topics and will hopefully help the allergist in clinical practice. Parietaria allergy is an intriguing challenge for the allergist in clinical practice, but it may be adequately managed by knowing the peculiarities of respective territories and the clinical characteristics of each patient.