The introduction of non-native organisms has caused changes in island ecosystems world-wide. Two of the main drivers of island extinctions and ecosystem changes are goats and black rats. These organisms alter considerably the flora of island ecosystems by limiting propagule production and dispersal as well as constant herbivory. Even so, island floras can still be diverse if human contact is limited and removal of non-native organisms is carried out. This can start regeneration of the damaged ecosystem and begin the process of ecosystem restoration. The goal of our research was to update the flora of the island from the last 16 or more years. Plants were opportunistically observed, and some collected along trails, ridges, coastal areas, and in the most accessible valleys where other restoration efforts were taking place. Each collected plant was identified in the field, photographed, described, and its GPS coordinates were recorded. A total of 69 species were observed in the field, 17 of which were collected and vouchered in the UPR-Mayagüez Herbarium. Populations of some native plants, such as Harrisia portoricensis Britton (Cactaceae) seemed to be abundant while others, such as the Mammillaria nivosa Link. (Cactaceae) were found in marginal areas with a highly-restricted population. New populations of previously unknown non-natives Spathodea campanulata P. Beauv. (Bignoniaceae), Cenchrus ciliaris L. (Poaceae), and Leucaena leucocephala (Lam.) de Wit (Fabaceae) in Desecheo are of conservation concern. Control or quick removal of these invasive species would help the restoration process of the island.