Ca 2+ signaling in neurons is intimately associated with the regulation of vital physiological processes including growth, survival and differentiation. In neurons, Ca 2+ elicits two major functions. First as a charge carrier, Ca 2+ reveals an indispensable role in information relay via membrane depolarization, exocytosis, and the release of neurotransmitters. Second on a global basis, Ca 2+ acts as a ubiquitous intracellular messenger to modulate neuronal function. Thus, to mediate Ca 2+-dependent physiological events, neurons engage multiple mode of Ca 2+ entry through a variety of Ca 2+ permeable plasma membrane channels. Here we discuss a subset of specialized Ca 2+-permeable non-selective TRPC channels and summarize their physiological and pathological role in the context of excitable cells. TRPC channels are predominately expressed in neuronal cells and are activated through complex mechanisms, including second messengers and store depletion. A growing body of evidence suggests a prime contribution of TRPC channels in regulating fundamental neuronal functions. TRPC channels have been shown to be associated with neuronal development, proliferation and differentiation. In addition, TRPC channels have also been suggested to have a potential role in regulating neurosecretion, long term potentiation, and synaptic plasticity. During the past years, numerous seminal discoveries relating TRPC channels to neurons have constantly emphasized on the significant contribution of this group of ion channels in regulating neuronal function. Here we review the major groundbreaking work that has uniquely placed TRPC channels in a pivotal position for governing neuronal Ca 2+ signaling and associated physiological responses.