Since the times of Rokitansky and Cushing, we have been fascinated by the connections between the gut and the brain. Recent advances in next-generation sequencing techniques have shown that this relationship is even more complex and integral to our sense of self than previously imagined. As these techniques refine our understanding of the abundance and diversity of the gut bacterial microbiome, the relationship between the gut and the brain has been redefined. Now, this is understood as a complex symbiotic network with bidirectional communication, the gut-brain axis. The implication of this communication involves an intense focus of research on a variety of chronic psychiatric, neurological, neurodegenerative, and neuro-oncological diseases. Recently, the gut-brain axis has been studied in neurologically ill patients requiring intensive care. Preliminary studies have shown that acute brain injury changes the bacterial phenotype from one that is symbiotic with the host human to one that is pathologic, termed the “pathobiome.” This can contribute to nosocomial pneumonia and sepsis. The first studies in neurologically ill patients in the neurointensive care unit (NeuroICU) demonstrated changes in the gut microbiome between neuroICU patients and healthy matched subjects. Specifically, a decrease in short-chain fatty acid-producing bacteria and increase in harmful gut microbes have been associated with mortality and decreased function at discharge. Although these preliminary findings are exciting and have opened a new field of research in the complex NeuroICU population, there are several limitations and challenges. Further investigation is needed to confirm these correlations and understand their implications on patients in a complex intensive care environment.