Dengue is a mosquito-transmitted viral infectious disease that is endemic to 110 countries spanning tropical and subtropical regions. While infection is typically asymptomatic, symptoms of the estimated 50-100 million clinical cases are often debilitating and occasionally life-threatening, resulting in as many as 5 million hospitalisations annually. Consequently, the World Health Organization regards dengue as a significant global public health concern. Immense challenges exist in both formulating and constructing an efficacious vaccine for prophylaxis and in developing therapeutics for cure. Although there have been numerous molecular studies of the interaction between host and virus, and the metabolic pathways of several proteins are implicated in dengue virus replication, their biological significance remains unclear. It is important to consider clinical, immunopathological and epidemiological features to decipher the complexity of disease and to unravel the mechanisms attributed to its progression. This editorial emphasises the critical events causing vascular endothelial permeability, which underpins the manifestations in humans of dengue haemorrhagic fever and dengue shock syndrome.