The large-conductance voltage and calcium-sensitive BK channel is important in many electrically active cells. Its unique sensitivity to both intracellular calcium levels and membrane potential makes it a key regulator of intracellular calcium, a critical second messenger in cells. The BK channel is expressed ubiquitously in the body and has particularly significant roles in the neuronal and smooth muscle cells. More recently, the importance of BK channel in the pathophysiology of hypertension has been demonstrated. In this review, we will focus on function, regulation, and clinical significance of the BK channel. We will also specifically concentrate on one of its β-subunits, β1, which is important in vascular and renal physiology.