Immune response relies upon several intracellular signaling events. Among the protein kinases involved in these pathways, members of the protein kinase C (PKC) family are prominent molecules because they have the capacity to acutely and reversibly modulate effector protein functions, controlling both spatial distribution and dynamic properties of the signals. Different PKC isoforms are involved in distinct signaling pathways, with selective functions in a cell-specific manner.In innate system, Toll-like receptor signaling is the main molecular event triggering effector functions. Various isoforms of PKC can be common to different TLRs, while some of them are specific for a certain type of TLR. Protein kinases involvement in innate immune cells are presented within the chapter emphasizing their coordination in many aspects of immune cell function and, as important players in immune regulation.In adaptive immunity T-cell receptor and B-cell receptor signaling are the main intracellular pathways involved in seminal immune specific cellular events. Activation through TCR and BCR can have common intracellular pathways while others can be specific for the type of receptor involved or for the specific function triggered. Various PKC isoforms involvement in TCR and BCR Intracellular signaling will be presented as positive and negative regulators of the immune response events triggered in adaptive immunity.