Dengue is emerging as one of the most abundant vector-borne disease globally. Although the majority of infections are asymptomatic or result in only a brief systemic viral illness, a small proportion of patients develop potentially fatal complications. These severe manifestations, including a unique plasma leakage syndrome, a coagulopathy sometimes accompanied by bleeding, and organ impairment, occur relatively late in the disease course, presenting a window of opportunity to identify the group of patients likely to progress to these complications. However, as yet, differentiating this group from the thousands of milder cases seen each day during outbreaks remains challenging, and simple and inexpensive strategies are urgently needed in order to improve case management and to facilitate appropriate use of limited resources. This review will cover the current understanding of the risk factors associated with poor outcome in dengue. We focus particularly on the clinical features of the disease and on conventional investigations that are usually accessible in mid-level healthcare facilities in endemic areas, and then discuss a variety of viral, immunological and vascular biomarkers that have the potential to improve risk prediction. We conclude with a description of several novel methods of assessing vascular function and intravascular volume status non-invasively.