Over geologic time, the water in the Bonneville basin has risen and fallen, most dramatically as freshwater Lake Bonneville lost enormous volume 15,000–13,000 years ago and became the modern day Great Salt Lake. It is likely that paleo-humans lived along the shores of this body of water as it shrunk to the present margins, and native peoples inhabited the surrounding desert and wetlands in recent times. Nineteenth century Euro-American explorers and pioneers described the geology, geography, and flora and fauna of Great Salt Lake, but their work attracted white settlers to Utah, who changed the lake immeasurably. Human intervention in the 1950s created two large sub-ecosystems, bisected by a railroad causeway. The north arm approaches ten times the salinity of sea water, while the south arm salinity is a meager four times that of the oceans. Great Salt Lake was historically referred to as sterile, leading to the nickname “America’s Dead Sea.” However, the salty brine is teaming with life, even in the hypersaline north arm. In fact, scientists have known that this lake contains a diversity of microscopic lifeforms for more than 100 years. This essay will explore the stories of the people who observed and researched the salty microbiology of Great Salt Lake, whose discoveries demonstrated the presence of bacteria, archaea, algae, and protozoa that thrive in this lake. These scientists documented the lake’s microbiology as the lake changed, with input from human waste and the creation of impounded areas. Modern work on the microbiology of Great Salt Lake has added molecular approaches and illuminated the community structures in various regions, and fungi and viruses have now been described. The exploration of Great Salt Lake by scientists describing these tiny inhabitants of the brine illuminate the larger terminal lake with its many facets, anthropomorphic challenges, and ever-changing shorelines.