Understanding plant resistance to pathogenic microbes requires detailed information on the molecular mechanisms controlling the execution of plant innate immune responses. A growing body of evidence places phosphoinositide-specific phospholipase C (PI-PLC) enzymes immediately downstream of activated immune receptors, well upstream of the initiation of early defense responses. An increase of the cytoplasmic levels of free Ca2+, lowering of the intercellular pH and the oxidative burst are a few examples of such responses and these are regulated by PI-PLCs. Consequently, PI-PLC activation represents an early primary signaling switch between elicitation and response involving the controlled hydrolysis of essential signaling phospholipids, thereby simultaneously generating lipid and non-lipid second messenger molecules required for a swift cellular defense response. Here, we elaborate on the signals generated by PI-PLCs and their respective downstream effects, while providing an inventory of different types of evidence describing the involvement of PI-PLCs in various aspects of plant immunity. We project the discussed information into a model describing the cellular events occurring after the activation of plant immune receptors. With this review we aim to provide new insights supporting future research on plant PI-PLCs and the development of plants with improved resistance.