The majority of kinase inhibitors that have been developed so far--known as type I inhibitors--target the ATP binding site of the kinase in its active conformation, in which the activation loop is phosphorylated. Recently, crystal structures of inhibitors such as imatinib (STI571), BIRB796 and sorafenib (BAY43-9006)--known as type II inhibitors--have revealed a new binding mode that exploits an additional binding site immediately adjacent to the region occupied by ATP. This pocket is made accessible by an activation-loop rearrangement that is characteristic of kinases in an inactive conformation. Here, we present a structural analysis of binding modes of known human type II inhibitors and demonstrate that they conform to a pharmacophore model that is currently being used to design a new generation of kinase inhibitors.