Historically, mammalian caspases (a group of cysteine proteases) have been catalogued into two main families based on major biological function: inflammatory caspases and apoptotic caspases. Accumulating evidence from preclinical models, however, argues against such a clearcut distinction, for two main reasons. First, at least in mammals, apoptotic caspases are generally dispensable for cells to succumb to apoptotic stimuli but instead regulate the kinetic and microenvironmental manifestations of the cellular demise in the context of a complex interplay with other cell death pathways. Second, most (if not all) mammalian caspases have evolved into positive or negative regulators of inflammatory processes, either directly or via their ability to control apoptotic and non-apoptotic cell death modalities. Here we discuss the molecular mechanisms through which mammalian caspases regulate inflammation, with emphasis on the ability of apoptotic caspases to suppress inflammatory responses in support of preserved organismal homeostasis.