Honeybees (HB) are essential for production of many food crops. Yet, they are under pressure globally, with Varroa destructor (Vd), its vectored viruses, and Nosema ceranae (Nc), being implicated as major stressors. The worldwide invasion of Vd and Nc in a few decades implies that there is little knowledge about prevalence, loads, and diversity of HB viruses and Nosemosis prior to both invasions. There are only a few Vd-free and possibly even fewer Nc-free refuges in the World, with the Azores archipelago being one. The Azores has, not only islands with and without Vd and Nc, but also harbors a genetically complex HB, enabling unprecedented analyses of host-pathogen interactions and of changes in epidemiological patterns in response to invasions. The Azores is, thereby, a unique location in which to study the most important drivers of HB decline. Expected findings from this study will, not only greatly advance current knowledge on emerging diseases, but also stimulate beekeeping in the Azores.