Interleukin (IL)-1 is a pivotal pro-inflammatory cytokine and an important mediator of both acute and chronic central nervous system (CNS) injuries. Despite intense research in CNS IL-1 biology over the past two decades, its precise mechanism of action in inflammatory responses to acute brain disorders remains largely unknown. In particular, much effort has been focussed on using in vitro approaches to better understand the cellular and signalling mechanisms of actions of IL-1, yet some discrepancies in the literature regarding the effects produced by IL-1β in in vitro paradigms of injury still exist, particularly as to whether IL-1 exerts neurotoxic or neuroprotective effects. Here we aim to review the cell-specific and concentration-dependent actions of IL-1 in brain cells, to depict the mechanism by which this cytokine induces neurotoxicity or neuroprotection in acute brain injury.