The endothelium plays a key role in regulating the progression and metastasis of tumours. The blood vessels not only deliver oxygen and nutrients to tumours but also provide the pathway for cancerous cells to metastasise. The formation of new blood vessels (angiogenesis) is crucial for tumour growth, progression, and metastasis. Endothelial cells (ECs) form new blood vessels by migrating and proliferating towards the tumour, following pro-angiogenic signals. The crosstalk between ECs and tumour cells in the tumour microenvironment is essential for tumour development and progression. When compared to normal ECs, tumour-associated ECs exhibit different characteristics and could be a key therapeutic target. Understanding the role of ECs and their interactions with the tumour cells can help in the implementation of new therapeutic regimes for the management of tumours. Disruption of the EC-tumour cell interactions might be an effective strategy for cancer therapy. In this chapter, the role of ECs in tumour angiogenesis and cancer progression, endothelial-tumour cell communication in tumour microenvironment, and endothelial malignancies and dysregulation of EC signalling pathways are presented.