In situ conservation is widely considered a primary conservation strategy. Plant translocation, specifically, represents an important tool for reducing the extinction risk of threatened species. However, thus far, few documented translocations have been carried out in the Mediterranean islands. The Care-Mediflora project, carried out on six Mediterranean islands, tackles both short- and long-term needs for the insular endangered plants through in situ and ex situ conservation actions. The project approach is based on using ex situ activities as a tool to improve in situ conservation of threatened plant species. Fifty island plants (representing 45 taxa) were selected for translocations using common criteria. During the translocations, several approaches were used, which differed in site selection method, origin of genetic material, type of propagative material, planting method, and more. Although only preliminary data are available, some general lessons can be learned from the experience of the Care-Mediflora project. Among the factors restricting the implementation of translocations, limited financial resources appear to be the most important. Specific preliminary management actions, sometimes to be reiterated after translocation, increase the overall cost, but often are necessary for translocation success. Translocation using juvenile/reproductive plants produces better results over the short term, although seeds may provide good results over the long run (to be assessed in the future). Regardless, plant translocation success can only be detected over long periods; therefore, proper evaluation of plant translocations requires a long-term monitoring protocol. Care-Mediflora project represents the first attempt to combine the existing approaches in a common plant conservation strategy specifically focusing on the Mediterranean islands.