High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges. (Gut Liver 2010;4(Suppl. 1):S57-61)