Dendritic cells (DCs) surface, like all mammalian cells, is covered by proteins and lipids that are glycosylated. The attached glycan chains are complex structures with a high content of sialic acids. These sugars usually occupy a terminal position, thus representing key structural determinants for a number of receptors, such as lectins, and are potential modulators of DC responses. DCs are crucial players as innate and adaptive immune responses linkers, and have been exploited, with limited success, as therapeutic tools to trigger immunity against tumours or pathogens. However, an unmet clinical need is finding means to shape DC immune functions, to improve and diverse its applicability. This chapter will focus on the regulation of sialylation and sialic acid patterns in DC development and maturation and on evidences of DC immune responses modulation by sialic acids. Recently known roles of sialylation in specialized processes, such as endocytosis, recruitment, capacity for T cell priming and pathogen and tumour cell recognition, are herein reviewed. The study of DC sialome and its relevance is a work in progress, with promising implications for DC biology and therapeutic applications.