Abstract: Leptospirosis, caused by pathogenic spirochetes of the genus Leptospira, affects both humans and animals and is among the most common but neglected direct zoonotic disease in the world, particularly in untreated or undiagnosed animals as well as humans. Now, it has been considered as a re-emerging disease causing global health problem due to its increasing incidences in developing as well as developed nations. It is a multisystemic disease leading to death. Diagnostic tests of importance are Latex Agglutination Test (LAT), lateral flow and immunoglobulin M (IgM) based ELISA, PCR based assays, Multiple-microscopic Agglutination Test (MAT), Loop-mediated Isothermal Amplification (LAMP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Molecular tools like PCR-RFLP, real-time PCR, multiplex PCR, qPCR and immunocapture PCR have all been found useful for rapid and confirmatory detection and differentiation of pathogenic and non-pathogenic leptospires. Inactivated/killed and attenuated vaccines are always attempted, since the beginning of vaccine and vaccination story, against all emerging pathogens with mixed success stories. The advanced tools and techniques like recombinant DNA technology, reverse genetics, DNA vaccination, molecular genetics and proteomics approaches are being explored for search of novel antigens, proteins and genes as potential candidates to discover safer, efficient and better vaccines for leptospirosis. The present review highlights the leptospirosis, susceptible population, disease transmission and epidemiology, treatment, trends and advances in diagnosis, vaccines and vaccination strategies in humans and animals with a view to combat this organism having public health significance.