We are living in the Anthropocene, the human-dominated era in which anthropogenic activities are dramatically threatening ecosystem biodiversity and natural resource consumption. This Special Issue aims to host researchers’ contributions to the exploitation of microbial resources to face Anthropocene-driven issues, including improving sustainable agriculture practices, sustaining aquatic and terrestrial ecosystem biodiversity, promoting pollutant clean-up, counteracting antibiotic resistance spread, and coping with climate change’s impact on biogeochemical cycles and soil fertility loss.