There is increasing evidence for the existence of unique ecosystems that are dominated by locally adapted microbiota which harbour distinct lineages and biological capabilities, much like the macrobiota of Darwin's Galapagos Islands. As a primary example of such a system, we highlight key discoveries from the Cuatro Ciénegas basin in Mexico. We argue that high microbial endemism requires a combination of geographical isolation, long-term continuity and mechanisms for reducing the intensity of horizontal gene transfer (HGT). We also propose that strong phosphorus limitation has an important role in microbial diversification by reducing the intensity of HGT.