Background: Yellow fever is a severe and often fatal illness caused by Flavivirus. Yellow fever is endemic in tropical and subtropical regions of South America and Africa. The present study has highlighted the urgent requirement for an effective vaccination drive to be implemented in areas with the potential of an endemic outbreak. Vaccination is the best way to prevent yellow fever, especially for people traveling to affected areas. The yellow fever vaccine is highly effective; protection usually begins by the 10^th day after vaccine administration in 95% of people.  The vaccine has been reported to last for at least 10 years, and a single dose is now considered to confer lifelong immunity against yellow fever disease by the WHO. The attenuated vaccine strain 17D of the yellow fever virus is commonly used in research laboratories to study the virus and develop antiviral therapies. The vaccine strain is weakend and does not cause human disease, making it safe for laboratory settings without requiring high-level microbiological containment facilities. In particular, the vaccine strain is used to evaluate the inhibitory effect of compounds on yellow fever virus Vero cells. Vero cells are a type of monkey kidney cells that are commonly used in virus culture and antiviral research. Researchers can screen many compounds using vaccine strains, and cells identify potential antiviral agents against the yellow fever virus. Despite these challenges, several vaccines have undergone preclinical and clinical testing on humans. The group of vaccines includes vaccines that are like viral particles, DNA-based vaccines, entire virus recombinant vaccines, vaccines with origins in incompetent replication, attenuated vaccines, and vaccines with origins in competent copy. In conclusion, developing an effective yellow fever vaccine is crucial in containing the upsurge of the disease. The current review discussed several challenges in creating such a vaccine, progress has been made in recent years, and the current outlook is promising. Further, appropriate post-authorization and surveillance may be crucial factors in monitoring the vaccine's safety and efficacy in real-world settings.