Multiheme cytochromes c are widespread among prokaryotes, where they contribute to key steps in diverse biogeochemical cycles of the elements such as nitrogen, sulfur and iron. It was recently shown that these enzymes predominantly evolve by grafting and pruning of different modules of cytochrome domains instead of a gradual accumulation of mutations [1]. In a survey of multiheme cytochromes c from the Desulfuromonadia class of bacteria it was shown that evolution led to greater diversification of multiheme cytochromes predicted to be located in the extracellular space at the surface of the cells when compared with multiheme cytochromes predicted to be associated with the inner membrane [2]. On the one hand, this reflects the fact that multiheme cytochromes exposed to the extracellular environment are the product of adaptation to distinct conditions according to the particular ecosystem where the organism is found. On the other hand, multiheme cytochromes attached to the inner membrane are exposed to an environment that is less diverse because it involves the interaction with conserved molecular partners, namely the quinone pools, which diminishes the drive for diversification. Here I will present recent data obtained from diverse multiheme cytochrome c families, showing that gain and loss of heme c binding domains occur by distinct mechanisms that reflect the asymmetric complexity of making a viable heme c binding motif from scratch versus the single point mutation that disables one such motif. Overall, this work provides closure to the picture of how multiheme cytochromes c evolved to achieve the diversity of structures and functions found in nature.