Stinging jellyfish outbreaks represent a health hazard, causing contact dermatitis and systemic reactions. This study investigated the epidemiology, severity, and treatment protocols of jellyfish stings in a coastal area with high tourist development and frequent stinging jellyfish outbreaks of the central Mediterranean (Salento, Southern Italy), and the associated costs for the Italian National Health Service. In 2007-2011, 1,733 bathers (mostly children and females) sought medical assistance following jellyfish stings, the main cause of human pathologies due to contact with marine organisms. The majority of events were reported in the years 2007-2009, whereas the occurrence of cnidarian jellyfish outbreaks has been increasingly reported in the same area since summer 2010. Most symptoms were limited to local and cutaneous reactions; conversely, 8.7% of cases evoked complications, mainly due to allergic reactions. The main drugs used were corticosteroids, locally applied and systemic (46% and 43%, respectively), and with ammonia (74%) as the main non-pharmacological treatment. The estimated cost of jellyfish-related first-aid services along the Salento coastline over the 5-year period was approximately 400,000 Euros. Therefore the management of jellyfish outbreak phenomena need coordinated research efforts towards a better understanding of underlying ecological mechanisms, together with the adoption of effective prevention policy, mitigation strategies, and appropriate planning of health services at tourist hot spots.