Transient Receptor Potential channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by increasing cellular Ca(2+). In this review we focus on the roles of these channels in: (i) cell death (ii) proliferation and differentiation and (iii) transmitter release. Cell death: Ca(2+) influx participates in apoptotic and necrotic cell death. The Ca(2+) permeability and high sensitivity of part of these channels to oxidative/metabolic stress make them important participants in cell death. Several examples are given. Transient Receptor Potential Melastatin 2 is activated by H(2)O(2), inducing cell death through an increase in cellular Ca(2+) and activation of Poly ADP-Ribose Polymerase. Exposure of cultured cortical neurons to oxygen-glucose deprivation, in vitro, causes cell death via cation influx, mediated by Transient Receptor Potential Melastatin 7. Metabolic stress constitutively activates the Ca(2+) permeable Transient Receptor Potential channels of Drosophila photoreceptor in the dark, potentially leading to retinal degeneration. Similar sensitivity to metabolic stress characterizes several mammalian Transient Receptor Potential Canonical channels. Proliferation and differentiation: The rise in cytosolic Ca(2+) induces cell growth, differentiation and proliferation via activation of several transcription factors. Activating a variety of store operated and Transient Receptor Potential channels cause a rise in cytosolic Ca(2+), making these channels components involved in proliferation and differentiation. Transmitter release: Transient Receptor Potential Melastatin 7 channels reside in synaptic vesicles and regulate neurotransmitter release by a mechanism that is not entirely clear. All the above features of Transient Receptor Potential channels make them crucial components in important, sometimes conflicting, cellular processes that still need to be explored.