Leptospirosis is a zoonosis disseminated around the world, affecting about 160 wild and domestic species, which are latent reservoirs and a main source of contamination for humans. This zoonosis is caused by Leptospira sp., Gram-negative bacteria have the ability to survive in the urine. In addition, the impact in Public Health is given for the presence of puddles, ponds and standing water that are easily contaminated and that is become a permanent focus of transmission. Leptospirosis is diagnosed by using the conventional technique microglutinación (MAT). However, there are no standardized criteria of titles considered positive, resulting in a significant number of positives and negatives false. Therefore, it is necessary to evaluate new diagnostic strategies highly sensitive and specific to achieve a reliable and accurate diagnosis. This article seeks to review the role of proteins associated with pathogenicity and utility of gene expression studies in the implementation of new diagnostic techniques that allow postulating molecular markers of infection.