Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have provided new alternatives for minimally invasive treatment of gastrointestinal adenomas and early-stage cancers that involve a minimum risk of lymph-node metastasis. The use of submucosal injections is essential to the success of these endoscopic resection techniques. The "ideal" submucosal injection solution should provide a sufficiently high submucosal fluid cushion for safe and effective EMRs and ESDs while also preserving lesion tissue for accurate histopathological assessment. In the past, normal saline (NS) solution was commonly used for this purpose, but it is difficult to achieve the proper submucosal elevation and maintain the desired height with NS. Therefore, other safe and effective facilitative submucosal injection solutions have been developed that also take into account relevant cost-benefit considerations. This review examines recent advances in the development of effective submucosal injection solutions for use during endoscopic resections.