Dengue viruses (DENV), a group of four serologically distinct but related flaviviruses, are the cause of one of the most important emerging viral diseases. DENV infections result in a wide spectrum of clinical disease including dengue haemorrhagic fever (DHF), a viral haemorrhagic disease characterised by bleeding and plasma leakage. The characteristic feature of DHF is the transient period of plasma leakage and a haemorrhagic tendency. DHF occurs mostly during a secondary DENV infection. Serotype cross-reactive antibodies and mediators from serotype cross-reactive Dengue-specific T cells have been implicated in the pathogenesis. A complex interaction between virus, host immune response and endothelial cells likely impacts the barrier integrity and functions of endothelial cells leading to plasma leakage. Recently the role of angiogenic factors and the role of dengue virus on endothelial cell transcription and functions have been studied. Insights into the mechanisms that confer protection or cause disease are critical in the development of prophylactic and therapeutic modalities for this important disease.