The incidence and prevalence of pancreatic tumors, both solid and cystic, has increased over the last few years, mainly related to the diffusion and use of imaging methods, among them endoscopic ultrasound (EUS). EUS is not only an excellent diagnostic tool but also a great therapeutic tool, for example in drainage techniques and for guiding different types of local treatment. This chapter reviews the available data on the techniques and potential role of EUS-guided therapy in patients with cystic pancreatic lesions (CPLs). Two main methods of EUS-guided therapy for CPL have been tested, radiofrequency ablation and the delivery of different chemical agents. An important advantage of the ablative approach is treatment durability over time, that is, the long-term response. The majority of patients with an effective ablation will also show elimination of detectable KRAS mutations. The main difficulty in recommending any treatment for a CPL is that accurate diagnosis and risk stratification are frequently difficult.