Methods, devices and systems wherein a penetrating catheter or other penetrating device is used to penetrate into a target blood vessel, and wherein the target vessel is dilated prior to the penetration so as to improve the imaging, aiming at and/or penetration into the target vessel. In one embodiment, a tissue penetrating catheter device that is useable to penetrate from a blood vessel in which it is positioned to a target vessel comprises a flexible catheter advanceable into the first blood vessel and a tissue penetrator lumen adapted to receive an operative tissue penetrator which is usable to penetrate from the blood vessel to the target vessel when properly aimed. An imaging transducer may be fixedly mounted on or within the penetrating catheter to provide an imaging signal from which an image of the target vessel can be obtained. A target vessel dilating catheter is inserted into the target vessel and used to dilate the target vessel prior to imaging, aiming of the penetrator at and/or puncture thereof. Such vessel dilating catheters may comprise one or more occlusion member(s) (e.g., one or two balloons) to block flow through the target vessel and/or to isolate and pressurize a region of the vessel. Alternatively, the dilating catheter may comprise a dilating member that expands within the target vessel to cause a portion of the target vessel wall to enlarge, stretch, expand, bulge or otherwise dilate.