Potassium channel openers are a class of chemically heterogeneous compounds that produce vasodilatation by opening vascular smooth muscle potassium channels. Using various configurations of the powerful patch clamp technique, the molecular pharmacology of potassium channel openers has been largely explored in different cellular systems. These studies have revealed that the primary molecular target for potassium channel openers is this class of potassium channel proteins that close under the influence of intracellular ATP and have thus been named ATP sensitive potassium channels. Direct recordings of unitary ATP sensitive potassium channels in cell detached membrane patches support the view that potassium channel openers compete with intracellular ATP to prevent channel inhibition. However, there also exists experimental evidence that contradicts the competition hypothesis and suggests the involvement of phosphorylation-dephosphorylation mechanisms. The aim of the present article is to review experimental data that support, or inversely, contradict the potassium channel opener-ATP competition theory.