The tremendous diversity in eukaryotic life forms can ultimately be traced back to evolutionary modifications at the level of molecular networks. Deep understanding of these modifications will not only explain cellular diversity, but will also uncover different ways to execute similar processes and expose the evolutionary 'rules' that shape the molecular networks. Here, we review the evolutionary dynamics of the spindle assembly checkpoint (SAC), a signaling network that guards fidelity of chromosome segregation. We illustrate how the interpretation of divergent SAC systems in eukaryotic species is facilitated by combining detailed molecular knowledge of the SAC and extensive comparative genome analyses. Ultimately, expanding this to other core cellular systems and experimentally interrogating such systems in organisms from all major lineages may start outlining the routes to and eventual manifestation of the cellular diversity of eukaryotic life.