Guidewires underlie the entirety of endovascular tools and technology. Before any endovascular device or imaging catheter can be delivered into a vessel to treat a lesion, access must be established with a passage of a wire along which these devices are carried. The scope of available guidewires is vast, ranging from large, stiff wires to carry large endografts, to fine, complexly constructed wires for traversing atherosclerotic occlusions. Because of this, a fundamental understanding of wire use, construction, and properties is essential for choosing the best wire for the job. This chapter discusses how guidewires are used in clinical practice, with further emphasis on the finer details of their construction and how that underlies their specific properties and their performance in the vasculature.