During microglia activation the levels of active caspase-3, caspase-7 and caspase-8 are increased, which leads to the transcription of proinflammatory cytokines and factors. As such, the induction of caspase activity in microglia can be used as a marker for activation. The use of sensitive and quantitative techniques has made it possible to reproducibly detect these low levels of active caspases. This chapter outlines the materials and methodology for three different ways to detect caspase activation in microglia.