As with studies of many cell types, investigations of vascular smooth muscle cells over the past twenty years have shown potassium channels to be the primary hyperpolarising drive on membrane potential. They have also revealed substantial diversity in potassium channel properties and heterogeneous expression between different vascular beds, and as the vasculature adapts to development and disease. Despite much work we only have a glimpse into the complexities of this hyperpolarising system. Nevertheless, there are some important facts known from the efforts of many different laboratories across the world- for example: K+ channels are necessary signal transduction elements in numerous vasodilatory responses, including those to nitric oxide. Subtypes of potassium channel have emerged as sensors of specific physiological signals – for example: BK-Ca senses intracellular calcium, K-NDP (the smooth muscle K-ATP variant) senses intracellular nucleotide diphosphates, inward rectifiers like Kir2.1 sense extracellular potassium, and delayed rectifiers like the Kv1 subunits sense myogenic and endothelin-evoked depolarisation. Although direct linkage of a potassium channel gene to vascular disease is lacking, there are intriguing associations of potassium channels with vascular abnormalities and indications that pharmacological agents targeted to potassium channels have, or might have, therapeutic benefit. For example: A blocker of the IK-Ca potassium channel suppresses smooth muscle proliferation, suggesting potential as an agent to suppress progression of neointimal hyperplasia or atherosclerosis. Experimental K-NDP potassium channel gene deletion evokes coronary vasoconstriction, conferring Prinzmetal-like angina on the mouse, which is consistent with the known anti-anginal properties of nicorandil – the K-NDP opener / nitric oxide donor. It has also emerged that Kv1 potassium channel expression is tailored to arterial calibre and down-regulates in the hypertensive rat, suggesting a role in regulating the myogenic set-point and thus in determination of the absolute value of blood pressure. These are important findings, but we do not know if potassium channels really have relevance to human vascular disease. Nor do we know the mechanisms by which vascular smooth muscle cells select specific members of the genomic potassium channel toolkit, or regulate the correct number of channels at the membrane. Over the past few years we have initiated studies to address these aspects of vascular biology. One focus has been on identifying transcription factors that bind and regulate potassium channel genes in vascular smooth muscle. In this regard we have, for example, discovered REST (repressor element-1 silencing factor) as a novel transcription factor of vascular smooth muscle that binds potassium channel genes and regulates their expression in blood vessels. We have also explored the role of potassium channels in failure of the human saphenous vein used as a coronary artery-bypass graft, a failure that occurs because of smooth muscle proliferation and migration into the lumenal space. The lecture will outline such recent findings in the context of general developments in the field.