Dengue is a vector-borne viral disease, caused by the Flavivirus, Dengue virus (DENV). About 400 million cases and 22000 deaths occur due to dengue throughout the world each year. It is reported in more than 100 countries in the tropics and subtropical regions. A positive-stranded enveloped RNA virus, DENV is principally transmitted by Aedes mosquitoes. It has four antigenically distinct serotypes DENV-1 to 4, with different genotypes, having three structural proteins and seven non-structural proteins. Clinical symptoms of dengue range from mild fever to severe Dengue Haemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS), with thrombocytopenia, leucopenia, and increased vascular permeability. Though primary infection causes activation of immune responses against that DENV serotypes, the severity of the disease in enhanced via heterotypic infection by various serotypes and also by antibody dependent enhancement (ADE). The first licensed DENV vaccine was tetravalent CYD Denvaxia, but it was not approved in all countries. Lack of suitable animal model, proper mechanistic study in pathogenesis and ADE, are the main hindrances in vaccine development. This review summarizes the current knowledge on DENV epidemiology, biology, disease etiology in the context of prevention and protection from dengue virus disease.