 Evolutionary biology has traditionally been considered as a historical discipline that provides explanations without giving predictions. ESB offers an opportunity to develop more detailed models of evolving genotype-phenotype relations and to explore whether some evolutionary pathways are predictable given enough information about the network structures, dynamic states, and environmental conditions. Unlike forward engineering in synthetic biology, the aim is not to shape new designs but to understand the possible trajectories of change under different conditions. That is, ESB goes beyond historical accounts in exploring the potential for evolvability or innovation—what some have called the ‘tinkering potential’ of system evolution (Koonin &amp; Wolf 2010). Research on evolvability can, however, also inform and inspire functional analysis and design in synthetic biology (Calvert &amp; Frow 2015; Lewens 2013). Thus, also in this context, the relation between biology and engineering must also be reexamined.