Streptococcus suis is a zoonotic pathogen causing important economic losses in swine production. The most commonly used antibiotics in swine industry are tetracyclines, beta-lactams, and macrolides. Resistance to these antibiotics has already been observed worldwide (reaching high rates for macrolides and tetracyclines) as well as resistance to aminoglycosides, fluoroquinolones, amphenicols, and glycopeptides. Most of the resistance mechanisms are encoded by antibiotic resistance genes, and a large part are carried by mobile genetic elements (MGEs) that can be transferred through horizontal gene transfer. This review provides an update of the resistance genes, their combination in multidrug isolates, and their localization on MGEs in S. suis. It also includes an overview of the contribution of biofilm to antimicrobial resistance in this bacterial species. The identification of resistance genes and study of their localization in S. suis as well as the environmental factors that can modulate their dissemination appear essential in order to decipher the role of this bacterium as a reservoir of antibiotic genes for other species.