Abstract: Systems and methods for positioning a wire for advancement through a vessel wall, and advancing it through one or more vessel walls, generally include a delivery catheter and an alignment catheter or a receiving catheter, and a guidewire. In some variations, the systems and methods may be used to bypass an occlusion or other barrier that may prevent advancement of a wire or tools through an endoluminal space. In these variations, the systems and methods include a delivery catheter, a bypass catheter, a receiving catheter, and a guidewire. The delivery and receiving catheters each generally include a side aperture, a deflection surface, and an alignment element, and the bypass catheter generally includes two side apertures, two deflectors, and two alignment elements. In some variations, the systems and methods may assist in treatment of a patient suffering from critical limb ischemia.