Our understanding of the biology of TRP channels has been hampered by a lack of specific and selective pharmacological tools with which to probe physiological function. Compounds, such as SKF 96365, have been extensively used to identify possible TRP channel mediated functions, but they have had limited impact in pharmacologically sub-dividing functional responses. The molecular characterisation of this diverse family of cation channels has now provided a set of targets on which to profile potential pharmacological probes and screen for new agents with better selectivity. Most success, to date, has been achieved with the TRPV1 channel where the early existence of agonist ligands and interest in this target as a route to new pain therapies has attracted substantial effort. New approaches initially shared structural features with the prototypic capsazepine, but the most recent patents disclose quite diverse templates. This demonstrates the success of functional high throughput screens in identifying a variety of novel chemical leads. These experiences with TRPV1, will encourage and aid more rapid development of novel ligands for other members of the TRP family.