Recent advances in chemical synthesis, conjugation chemistry, engineered biosynthesis, and formulation design have spawned a new generation of vaccines that incorporate carbohydrate antigens. By providing better immunity against a variety of pathogens or malignant cells and lowering the cost of production, these developments overcome many of the limitations associated with conventional vaccines involving polysaccharides. Moreover, the resulting vaccine candidates are shedding light on how the immune system responds to carbohydrates and providing mechanistic insight that can help guide future vaccine design. Here, we review recent engineering efforts to develop and manufacture carbohydrate-based vaccines that are efficacious, durable, and cost-effective.