Ca2+ elevation in the cytosol is an essential early event during pathogen response signaling cascades. However, the specific ion channels involved in Ca2+ influx into plant cells, and how Ca2+ signals are initiated and regulate downstream events during pathogen defense responses, are at present unclear. Plant cyclic nucleotide gated ion channels (CNGCs) provide a pathway for Ca2+ conductance across the plasma membrane (PM) and facilitate cytosolic Ca2+ elevation in response to pathogen signals. Recent studies indicate that the recognition of pathogens results in cyclic nucleotide production and the activation of CNGCs, which leads to downstream generation of pivotal signaling molecules (such as nitric oxide (NO)). Calmodulins (CaMs) and CaM-like proteins (CMLs) are also involved in this signaling, functioning as Ca2+ sensors and mediating the synthesis of NO during the plant pathogen response signaling cascade. In this article, these and other pivotal signaling components downstream from the Ca2+ signal, such as Ca2+-dependent protein kinases (CDPKs) and CaM-binding transcription activators (CAMTAs), are discussed in terms of their involvement in the pathogen response signal transduction cascade.