High-latitude meromictic lakes such as those in the Antarctic McMurdo Dry Valleys (MDV) harbor aquatic ecosystems dominated by the microbial loop. Within this habitat, which is limited year-round by light and nutrients, protists, or single celled eukaryotes, play outsized roles in the food web as the dominant primary producers and the apex predators. Thus, the MDV lake ecosystem represents an ideal system to study the role of sentinel protist taxa in carbon and nutrient cycling. The perennially ice-covered lakes are part of the McMurdo Long Term Ecological Research (McM LTER; mcmlter.org) established in 1993. In this review we will highlight the diversity and trophic roles of the MDV lake protist community and compare environmental factors driving spatiotemporal patterns in key protist taxa in two lakes within the McM LTER, Lakes Bonney and Fryxell. We will then discuss lessons learned from manipulated experiments on the impact of current and future climate-driven environmental change on sensitive protist taxa. Last, we will integrate knowledge gained from 25 years of lab-controlled experiments on key photosynthetic protists to extend our understanding of the function of these extremophiles within the MDV aquatic food webs. Our research group has studied the distribution and function of the MDV microbial community for nearly two decades, training the next generation of scientists to tackle future problems of these globally significant microbes. This review article will also highlight early career scientists who have contributed to this body of work and represent the future of scientific understanding in the Anthropocene.