The physiological function and cellular role of some members of the TRPM family are poorly understood and still mysterious. Melastatin, the founding member of the TRPM group, is the most prominent example of the mysteries involved in understanding TRP channel function. Melastatin or TRPM1 was first cloned in 1998 and since then it has been suggested that it functions as a tumor suppressor protein in melanocytes. On the other hand, TRPM8 and TRPA1 have been described as cold receptors, TRPM4 and TRPM5 as calcium-activated nonselective cation channels, TRPM6 and TRPM7 as magnesium-permeable and magnesium-modulated cation channels, TRPM2 as an ADP-ribose-activated channel of macrophages, and TRPM3 as a hypo-osmolarity- and sphingosine-activated channel. There are many unsolved questions and many studies have to be performed to understand the overall function of the TRPM family. In addition to electrophysiological recordings and biochemical characterization, the use of compounds modulating TRPM channel function has often been helpful to study TRPM channels in a cellular context. Therefore, the review will summarize the known functions, activation mechanisms, and pharmacological modulations of the TRPM channels.