Streptococcus suis ranks among the key bacterial pathogens with high prevalence causing significant economic impacts in the swine sector, as the global trend shifts away from prophylactic antimicrobial use. Moreover, it poses a major emerging zoonotic threat, impacting individuals in direct proximity to infected pigs or pork products. Besides certain Asian countries, S. suis is recognized as a significant public health concern globally affecting both livestock and human populations. The pathogen’s ability to spread through respiratory droplets, direct contact, or contaminated food products poses a risk to individuals involved in the swine industry and pork consumption. Moreover, the emergence of antibiotic-resistant strains complicates treatment and control measures. While previously viewed as sporadic incidences, human infections caused by this pathogen have been reported over the past four and a half decades, with two prominent outbreaks recorded in China in 1998 and 2005. These infections cause a range of complications, such as purulent meningitis, septic shock, endocarditis, pneumonic syndromes, uveitis-endophthalmitis, and arthritis in both pigs and human beings. Over the past few decades, ongoing efforts have led to significant advancements in our understanding of this zoonotic infectious organism, contributing to unveiling the molecular mechanisms that underlie its high pathogenicity. This chapter will offer background information on the biology and molecular characteristics of this Gram-positive bacterium, along with detailing the clinical signs, pathology, epidemiology, diagnosis, treatment, and prevention of the occurrence of the disease in both animals and humans.