The mammalian melastatin-related transient receptor potential (TRPM) subfamily contains eight members. TRPM proteins, consisting of six putative transmembrane domains and intracellular N and C termini, form monovalent-permeable cation channels with variable selectivity for Ca(2+), Mg(2+) and other divalent cations. Some functions are linked to their individual cation selectivity: the highly divalent-permeable cation channels TRPM6 and TRPM7 are involved in the control of Mg(2+) influx, whereas the Ca(2+)-impermeable channels TRPM4 and TRPM5 modulate cellular Ca(2+) entry by determining the membrane potential. TRPM2, TRPM3 and TRPM8 mediate a direct influx of Ca(2+) in response to specific stimuli. Electrophysiological properties of the founding member, melastatin (TRPM1), are unexplored. The individual TRPM members are activated by different stimuli, including voltage, Ca(2+), temperature, cell swelling, lipid compounds and other endogenous or exogenous ligands. This review summarizes molecular features, activation mechanisms, biophysical properties and modulators of TRPM channels.