Gut microbiomes have close relationships with their hosts, and their hosts’ health. One of the key mediators of this gut-host-health connection are microbially produced short-chain fatty acids (SCFAs). Microbes produce SCFAs from dietary fiber and host secretions. SCFAs can affect intestinal mobility, gut barrier function, and host metabolism, and, consequently, SCFAs play a role in numerous human diseases. A recent review describes the diverse roles of this class of bacterial metabolites and their ability to affect such diseases. While the diseases SCFAs affect include metabolic and intestinal diseases like diabetes, colitis, and colorectal cancer, they also affect diseases from other systems like pneumonia, chronic kidney disease, and even some neurologic disorders. The major SCFAs—acetate, propionate, and butyrate—influence immunity, apoptosis, inflammation, and lipid metabolism. Through those pathways and others, SCFAs may have therapeutic relevance. SCFA metabolism can be influenced through the microbiome via methods like fecal microbiota transplantation, probiotics, and prebiotics. Overall, SCFAs have many links to disease, but the mechanisms of this influence remain poorly understood. So, more research is needed to understand how best to influence SCFA production in an effort to treat or prevent disease.