One of the key aims of synthetic biology is to engineer artificial processes inside living cells. This requires components that interact in a predictable manner, both with each other and with existing cellular systems. However, the activity of many components is constrained by their interactions with other cellular molecules and often their roles in maintaining cell health. To escape this limitation, researchers are pursuing an "orthogonal" approach, building a parallel metabolism within the cell. Components of this parallel metabolism can be sourced from evolutionarily distant species or reengineered from existing cellular molecules by using rational design and directed evolution. These approaches allow the study of basic principles in cell biology and the engineering of cells that can function as environmental sensors, simple computers, and drug factories.