The Caatinga biome in Brazil is renowned for its rich aboveground biodiversity. However, approximately 19% of this biome has experienced desertification, severely affecting the soil microbiome. Monitoring these microbial communities is essential to understanding the impacts of desertification and the potential outcomes of restoration efforts. The Caatinga Microbiome Initiative aims to assess the soil microbiome in areas undergoing desertification and those under restoration in the Brazilian drylands. This initiative seeks to explore the core microbial communities and their functions, including overlooked groups such as protists, nematodes, and viruses across native, desertified, and restored areas. We believe that two approaches should be used simultaneously in the study of microbiomes in areas undergoing desertification. First, the use of the soil microbiome as a bioindicator of soil quality in both desertified and restored lands. Second, the manipulation of the microbiome to facilitate soil restoration. By understanding soil microbiome responses to desertification and restoration, we can develop targeted restoration strategies to enhance biodiversity and promote functional recovery in desertified areas.