The regulation of microvascular survival impacts both developmental remodeling of the vasculature, and various microvascular pathologies. In pathological settings of vascular insufficiency, molecular targets to affect stabilization of neovascularization are needed. Conversely, an important part of anti-tumor angiogenesis is the de-stabilization of the tumor vasculature. In the study of vascular remodeling, one difficult challenge is to understand the molecular controls that allow regression of one entire vessel segment and not another. This phenomenon requires coordination of the survival signaling pathways to successfully impact vascular structure. This review describes the known mechanisms and molecules involved in microvascular and endothelial cell survival. In particular the mechanisms of molecular signaling for survival in vitro are discussed in light of what is known about microvascular survival in vivo. Possible ways to bring these data together to explain the complex regulation of vessel survival are discussed.