ASIC channels are the simplest version of ligand-gated ion channels. Their ligand is the proton. There are 3 major genes for this channel family coding for ASIC1, ASIC2 and ASIC3 channels and there are spliced versions of these channels. ASIC channels assemble into homo or heterotrimers and are permeable to Na+ and, for some of them, to Ca2+. Different subunit assemblies have different biophysical properties (activation, inactivation, reactivation, pH-dependency …) and different physiological functions. These channels are highly expressed in the central as well as in the peripheral nervous system and beside their structure- function activity, their role will be particularly discussed in relation with pain. Local acidification is associated with most types of pain events. The presentation will show how the ASIC3 channel, because it is capable to sense very small pH variations, hyperosmolarity and many of the factors liberated in the course of inflammation, is a key channel for a large variety of pain states (inflammatory pain, post surgical pain …). It will also demonstrate the importance of the ASIC1a channel in the spinal chord and the spectacular effects of its blockade against all types of pain including neuropathic pain. The presentation will describe a series of venom peptides with a potent analgesic potential acting on ASIC3 or ASIC1a channels and will explain how they interact with ASIC channels and why they might become interesting drugs.