The definition of “xenobiology” has gradually shifted from the study of the foreign, estranged life forms potentially existing in outer space to the study where the natural and synthetic life are involved. The natural concept of xenobiology governs the unseen, hypothetical life on the outer space, and the hidden life with completely different biochemistry on Earth. The life on the outer space might possess different way to harvest energy from the one on Earth. The hidden life on Earth, or the “Shadow Biosphere” might rose from completely different way of creation and evolution on Earth, which lead to its complete difference from the known biosphere. The newest concept of xenobiology involves synthetic life, built with unnatural base pair of the nucleic acid, with analogous or xeno nucleic acid (XNA), has a synthetic genome which capable of self-replicating or enables the synthetic cell to self-replicate, or even possesses a synthetic physiological pathway. By understanding the broad spectrum of xenobiology, in both natural and synthetic concepts, we can expand our view on how life might develop into a completely estranged system, which is different from anthropocentric view of life available around us on Earth. From these perspectives, we might understand how life evolved by evolving it synthetically.