Methods and apparatus for delivery of substances or apparatus to target sites located outside blood vessel lumens. A penetrating catheter is inserted into a blood vessel lumen and a penetrator is advanced from the catheter in the direction of the target site. Thereafter, a delivery catheter is passed through a lumen of the penetrator to the target site. A desired substance or apparatus is then delivered to or obtained from the target site. In some applications, the delivery catheter may remain in place for chronic or continuous delivery of substance(s) to and/or obtaining of information or samples from the target site. Alternatively, a delivery catheter having an occlusion member may be advanced into a vein or venule and used to occlude the lumen of the vein or venule during and after injection of a substance such that the substance will not be carried away by normal venous blood flow.