Climate change will impact several ecosystems, and the resilience of the weakest links of the ecological networks may be decisive in maintaining the ecological structure. The assessment of tendencies in the distribution and resilience of endangered medicinal species against global change can be an excellent tool to predict and minimize future negative effects, even more so if we consider that these species may be useful to us. Spain is one of the richest countries in plant diversity along the Mediterranean basin, and many representatives of the Spanish flora are medicinal plants. Under scenarios of climate change, the distribution ranges of many of these species are likely to alter. In this paper we used ecological niche modeling to predict future changes in the distribution of 41 medicinal plants included in the 2013 assessment of threatened species in Spain. We generated climate-based niche models for each medicinal species and projected them for each decade from 2010 until 2080. Our results identified and prioritized the most vulnerable species and areas to future predicted changes. These results should be useful for conservation planning and especially for prioritizing areas for protection.