Infections caused by Streptococcus suis are considered a global problem in the swine industry. In this animal species, S. suis is associated with septicemia, meningitis, endocarditis, arthritis and, occasionally, other infections. Moreover, it is an agent of zoonosis that afflicts people in close contact with infected pigs or pork-derived products. Although sporadic cases of S. suis infection in humans have been reported, a large outbreak due to S. suis serotype 2 emerged in the summer of 2005 in Sichuan, China. A similar outbreak was observed in another Chinese province in 1998. Symptoms reported in these two outbreaks include high fever, malaise, nausea and vomiting, followed by nervous symptoms, subcutaneous hemorrhage, septic shock and coma in severe cases. The increased severity of S. suis infections in humans, such as a shorter incubation time, more rapid disease progression and higher rate of mortality, underscores the critical need to better understand the factors associated with pathogenesis of S. suis infection. From the 35 capsular serotypes currently known, serotype 2 is considered the most virulent and frequently isolated in both swine and humans. Here, we review the epidemiological, clinical and immunopathological features of S. suis infection in humans.