TRP channels participate in many cellular processes including cell death. These channels mediate these effects mainly by changing the cellular concentration of Ca2+, a prominent cellular second messenger. Measuring the current–voltage relationship and state of activation of TRP channels is of utmost importance for evaluating their contribution to a cellular process within a spatial and temporal context. The study of TRP channels and characterization of their mode of activation will benefit and progress our understanding of each channel’s role in specific cellular mechanisms. Many TRP channels exhibit constitutive activity, which is mostly observed in cell-based expression systems. This constitutive activity can lead, in many cases, to cellular degeneration, which can be readily observed morphologically and by biochemical assays. This chapter describes in brief different modes of TRP channel activity and their current–voltage relationships. The chapter outlines methods for visualizing this activity and methods to correlate between TRP channel activity and cell death, and it illustrates mechanisms that prevent cell death in spite of constitutive activity. Finally, it describes methods for qualitatively and quantitatively measuring the accompanied cellular degeneration.