The TRP superfamily of cation channels encompasses 28 mammalian members related to the product of the Drosophila trp (transient receptor potential) gene. TRP channels have a widespread distribution in many cell types and organs and gate in response to a broad variety of physical and chemical stimuli; as such, they can be considered as ubiquitous cellular sensors. Several recent studies reported modulation of different TRP channels by phosphoinositides, in particular by phosphatidylinositol 4,5-bisphosphate (PIP(2)). In most cases, PIP(2) promotes TRP channel activation. Here we provide a brief overview of current insights and controversies about the mechanisms and structural determinants of PIP(2)-TRP channel interactions, and zoom in on the regulation of the Ca(2+)- and voltage-gated TRPM4 by phosphoinositides.