Prokaryotic genomes of endosymbionts and parasites are examples of naturally evolved minimal cells, the study of which can shed light on life in its minimum form. Their diverse biology, their lack of a large set of orthologous genes and the existence of essential linage (and environmentally) specific genes all illustrate the diversity of genes building up naturally evolved minimal cells. This conclusion is reinforced by the fact that sometimes the same essential function is performed by genes from different evolutionary origins. Nevertheless, all cells perform a set of life-essential functions however different their cell machinery and environment in which they thrive. An upcoming challenge for biologists will be to discern, by studying differences and similarities in current biodiversity, how cells with reduced genomes have adapted while retaining all basic life-supporting functions.