Varicella Zoster Virus (VZV) poses particular challenges for individuals with compromised immune systems. Immunocompromised individuals, including those with HIV/AIDS, organ transplant recipients, and individuals undergoing immunosuppressive therapies, are at an increased risk of severe and disseminated VZV infections. Rather than the typical presentation of chickenpox, these individuals may experience a more severe and prolonged course of the disease, with the potential for visceral organ involvement. Preventing VZV infections in immunocompromised individuals is crucial, as they are more susceptible to complications. Vaccination before immunosuppression or the initiation of antiretroviral therapy is recommended to reduce the risk of primary VZV infection. Additionally, post-exposure prophylaxis with varicella-zoster immune globulin (VZIG) can be considered in certain situations. The reactivation of VZV, leading to shingles, also poses challenges for immunocompromised individuals. The prolonged and severe nature of shingles in this population emphasizes the importance of early diagnosis, antiviral treatment, and supportive care to minimize complications.