Upon microbial infection, cells of the innate immune system undergo profound metabolic reprogramming in order to eradicate pathogens, promote inflammation, and eventually restore tissue homeostasis. Mitochondria are at the core of these adaptations, given their dual role as metabolic hubs and innate immune signaling platforms. The mitochondrial electron transport chain (ETC) is very well characterized at the genetic, molecular, structural, and biochemical level. In contrast, the role for mitochondrial ETC and metabolites beyond fulfilling cellular ATP synthesis in innate immune cell biology was not understood until recently. Here we discuss the latest advances in our understanding of immune functions of mitochondria and particularly the mitochondrial respiratory chain.