Vitiligo pathogenesis is complex, involving genetic, environmental, and immunological factors. Various experimental models, including in vitro and animal models, have been established to elucidate disease mechanisms, immune responses, and potential therapeutic interventions. These models facilitate the study of cellular interactions, oxidative stress, cytokine involvement, and immune-mediated melanocyte destruction. Animal models play a crucial role in vitiligo research by replicating various aspects of the disease, which are difficult to incorporate into in vitro cultures. However, no single model fully represents human vitiligo, and the results must be interpreted cautiously. The most commonly used animal models are mice, which are developed through chemical induction (monobenzone and hydroquinone), immunization (recombinant melanocyte-specific antigens), or genetic modifications (involving antigen presentation). However, in vitro models are more precise and provide a controlled environment for studying melanocyte biology, immune interactions, and drug responses. These models are cost-effective, ethically favorable, and offer high reproducibility. Melanocytes, keratinocytes, and fibroblasts can be isolated from skin biopsies and cultured in specific growth medium in dishes in the laboratory. Altogether, both these models are indispensable in vitiligo research. While animal models provide a holistic view of disease progression, in vitro models enable mechanistic studies of melanocyte-immune interactions. Monobenzone- and interferon-induced models remain extensively used due to their relevance in studying vitiligo pathogenesis and therapeutic responses. Future research should be more focused on refining the existing models to enhance reproducibility and translational relevance. Advancements in vitiligo modeling will improve our understanding of disease mechanisms and accelerate the development of effective treatments.