Tissue-penetrating guidewires with shaped tips, and associated systems and methods are disclosed. A patient treatment system in accordance with one embodiment of the disclosure includes a tissue-penetrating guidewire that in turn includes a flexible segment having a distal portion and a proximal portion. The flexible segment is elongated along an elongation axis. A penetrating member is positioned at the distal portion and includes at least one blade segment having a tapered outer peripheral surface and an adjacent generally sharp edge. The blade segment extends to a distal end of the penetrating member to form a generally blunt tip. In operation, the guidewire can be connected to an electrical current source to deliver high frequency current to the penetrating member.
