Mycobacterium leprae and M. lepromatosis, the causative agents of leprosy, have left a mark on human history. Despite advances in health care, leprosy continues to affect millions worldwide, often leading to complications, mostly neural, due to delayed diagnosis and treatment. This persisting prevalence emphasizes the need for continued research and effective management strategies. Leprosy presents in many forms, mainly lepromatous and tuberculoid, influenced by the patient's immunological status and exhibits specific clinical characteristics. Studies have shown that Mycobacterium lepromatosis is frequently associated with the lepromatous forms of the disease, characterized by generalized skin lesions and systemic involvement. This connection has led to the distinction of M. lepromatosis as the main cause of Lucio Leprosy and Lucio phenomenon (LPh); this last one is an immune-mediated response, including necrotizing panvasculitis and systemic manifestations. Once considered endemic to Mexico and Central America, migration expanded its geographical reach. Triggers include infections and certain medical conditions. Histopathologically, LPh represents a necrotizing panvasculitis, ischemic necrosis, and the presence of immune components in small vessels. Diagnosis relies on clinical characteristics and histopathological findings. Treatment lacks standardization; however, effective management involves antileprosy medication and systemic glucocorticoids. In conclusion, the historical impact of leprosy and LPh persists in medical discussions. Prevention, early diagnosis, and treatment challenges continue, necessitating ongoing research to improve patient outcomes and bring down this health concern.