For over a decade the folate receptor has been intensively investigated as a means for tumor-specific delivery of a broad range of experimental therapies including several conceptually new treatments. Despite a few set backs in clinical trials, the literature is replete with encouraging in vitro and pre-clinical studies of gynecological and other tumors and more therapeutic approaches are ready for clinical testing. Recent studies have added myelogenous leukemias to the list of candidate cancers for FR-targeted therapies. Each approach faces unique challenges in translation that could be addressed through a mechanistic understanding of the function and expression of the receptor in the appropriate experimental systems and by improvements in the technology. This review discusses FR in the context of positive recent developments in broad areas of FR-targeted therapy and attempts to highlight its potential and the anticipated challenges.