Leptospirosis, an extensively occurring zoonotic disease instigated by pathogenic spirochetes belonging to the Leptospira genus, constitutes a major health hazard for both humans and animals on a global scale. This chapter presents a comprehensive overview of leptospirosis, covering its epidemiology, transmission dynamics, clinical features, diagnostic approaches, and preventive strategies. Humans can contract leptospirosis through either direct or indirect contact with the urine of infected animals, such as rodents, livestock, and wildlife. Environmental conditions, such as flooding and inadequate sanitation, are essential determinants of disease transmission. The clinical presentation of human leptospirosis involves a broad spectrum, from mild, influenza-like symptoms to severe, potentially life-threatening complications, such as Weil’s disease and pulmonary hemorrhage syndrome. This chapter emphasizes the diagnostic intricacies of leptospirosis owing to its nonspecific symptoms and the necessity of laboratory testing for definitive diagnosis. This chapter also highlights the crucial role of thorough disease monitoring systems, specific rodent control measures, and preventive approaches, such as vaccination initiatives and the use of personal protective gear, in effectively reducing and managing the spread of leptospirosis among both human and animal populations.