▪ Abstract A small number of prokaryotic species have a unique physiology or ecology related to their development of unusually large size. The biomass of bacteria varies over more than 10 orders of magnitude, from the 0.2 μm wide nanobacteria to the largest cells of the colorless sulfur bacteria, Thiomargarita namibiensis, with a diameter of 750 μm. All bacteria, including those that swim around in the environment, obtain their food molecules by molecular diffusion. Only the fastest and largest swimmers known, Thiovulum majus, are able to significantly increase their food supply by motility and by actively creating an advective flow through the entire population. Diffusion limitation generally restricts the maximal size of prokaryotic cells and provides a selective advantage for μm-sized cells at the normally low substrate concentrations in the environment. The largest heterotrophic bacteria, the 80 × 600 μm large Epulopiscium sp. from the gut of tropical fish, are presumably living in a very nutrient-rich medium. Many large bacteria contain numerous inclusions in the cells that reduce the volume of active cytoplasm. The most striking examples of competitive advantage from large cell size are found among the colorless sulfur bacteria that oxidize hydrogen sulfide to sulfate with oxygen or nitrate. The several-cm-long filamentous species can penetrate up through the ca 500-μm-thick diffusive boundary layer and may thereby reach into water containing their electron acceptor, oxygen or nitrate. By their ability to store vast quantities of both nitrate and elemental sulfur in the cells, these bacteria have become independent of the coexistence of their substrates. In fact, a close relative, T. namibiensis, can probably respire in the sulfidic mud for several months before again filling up their large vacuoles with nitrate.