Streptococcus suis is a major cause of respiratory tract and invasive infections in pigs and is responsible for a substantial disease burden in the pig industry. S. suis is also a significant cause of bacterial meningitis in humans, particularly in South East Asia. S. suis expresses a wide array of virulence factors, and although many are described as being required for disease, no single factor has been demonstrated to be absolutely required. The lack of uniform distribution of known virulence factors among individual strains and lack of evidence that any particular virulence factor is essential for disease makes the development of vaccines and treatments challenging. Here we review the current understanding of S. suis virulence factors and their role in the pathogenesis of this important zoonotic pathogen.