A comprehensive understanding of the biology of the vessel wall has fostered the discovery of novel therapeutic interventions. The vascular endothelium, smooth muscle cells, and adventitial fibroblasts exist in a tightly regulated milieu in which extravascular stimuli produce coordinated physiologic actions in each cell type, which, in turn, modulate integrative responses in the vessel wall. When vascular injury occurs as a result of biochemical or mechanical forces, such as in hypertension, atherosclerosis, or restenosis, normal homeostatic mechanisms are perturbed, and if compensatory mechanisms are overwhelmed, the vessel becomes dysfunctional. These states are characterized by changes in regulatory molecules that stimulate aberrant responses. Recent advances in molecular biology, including gene transfer and antisense technology, have been used successfully to replete or diminish these factors and restore vascular homeostasis. We present an overview of basic vascular biology as it relates to relevant clinical vascular pathobiology and molecular therapeutics.