In this article we present and discuss the main factors that threaten natural populations of Cypripedium calceolus (lady\'s slipper orchid) in Europe, and we propose conservation strategies and directions for protective actions of its population on a regional scale. European C. calceolus populations have decreased significantly in the last two decades, in both number and size. A key result of the present study is an evaluation of the effectiveness of the Natura 2000 network across the European Union (EU) countries. Northern and/or mountainous countries present higher percentages of potentially suitable areas within the Natura 2000 network. Finland and the United Kingdom are the exceptions to this rule. It is predicted that, due to global warming, the coverage of niches suitable for C. calceolus will decrease in countries in which now-healthy colonies exist. However, as plant species can occur in micro-sites with suitable environmental conditions (e.g., microclimate, vegetation, soil factors) which cannot be predicted as suitable at coarser spatial resolutions, conservation efforts should be focused on management of local healthy populations. For the effective protection of C. calceolus in Natura 2000 sites, the participation of experts in botany, including orchid biology, is necessary at several stages.