Abstract: Capsular polysaccharides and lipopolysaccharides are crucial bacterial virulence factors and key vaccine antigen targets. Over the past century, the development of bacterial polysaccharide-based vaccines has significantly advanced global efforts to prevent bacterial infections. This review outlines the historic milestones of bacterial polysaccharide vaccines, with an emphasis on the development and application of capsular polysaccharide-based vaccines against three human pathogens: Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Moreover, this article summarizes the protective mechanisms and perspectives of polysaccharide-based vaccines.