Endothelial cell (EC) apoptosis may play an important role in blood vessel development, homeostasis and remodelling. In support of this concept, EC apoptosis has been detected within remodelling vessels in vivo, and inactivation of EC apoptosis regulators has caused dramatic vascular phenotypes. EC apoptosis has also been associated with cardiovascular pathologies. Therefore, understanding the regulation of EC apoptosis, with the goal of intervening in this process, has become a current research focus. The protein-based signalling and cleavage cascades that regulate EC apoptosis are well known. However, the possibility that programmed transcriptome and glycome changes contribute to EC apoptosis has only recently been explored. Traditional bioinformatic techniques have allowed simultaneous study of thousands of molecular signals during the process of EC apoptosis. However, to progress further, we now need to understand the complex cause and effect relationships among these signals. In this article, we will first review current knowledge about the function and regulation of EC apoptosis including the roles of the proteome transcriptome and glycome. Then, we assess the potential for further bioinformatic analysis to advance our understanding of EC apoptosis, including the limitations of current technologies and the potential of emerging technologies such as gene regulatory networks.