Dengue is a vector-borne highly systemic infectious disease of the tropical and subtropical countries and is devastating millions of lives worldwide. It may be self-eliminated like a mild fever or may cause life-threatening fatal complications as dengue hemorrhagic fever and dengue shock syndrome. The lack of specific and effective antiviral drugs and vaccines amplify its transmission rate across the world. The development of the dengue vaccine has been an ambitious task due to the presence of four different dengue serotypes capable of carrying antibody enhancement complex mechanisms. In this review, we have summarized the ongoing challenges in the construction of a dengue vaccine and the current status of the vaccine development. Limited knowledge of immune responses against dengue infection, lack of human or animal model of disease, and suboptimal assay strategies to detect immune responses after infection or vaccination, are some barriers to vaccine and drug development. A tetravalent vaccine with low cost, high efficiency, and capable of eliciting immune responses against all four serotypes is needed to minimize the epidemics. Currently, only one live attenuated chimeric dengue vaccine, the CYD Dengue Vaccine, has completed its third phase and has been licensed. DENVax and TetraVax-DV-TV003 (TV003) are in the third phase while others are still in the first trial phase.