In multicellular organisms, the ligand-induced multiprotein complexes apoptosomes and inflammasomes are major players mediating apoptosis and inflammation, respectively. Both types of complexes function as a caspase-activating platform, but apoptosomes are specific for the apoptotic caspases such as caspase-9, whereas inflammasomes for inflammatory caspases like caspase-1. Here we summarize recent progresses on the molecular mechanisms underlying assembly and activation of the two types of protein complexes.