Coronavirus disease-19 (COVID-19) is a complex disorder caused by the pandemic diffusion of a novel coronavirus named SARS-CoV-2. Clinical manifestations vary from silent infection to severe pneumonia, disseminated thrombosis, multi-organ failure, and death. COVID-19 pathogenesis is still not fully elucidated, while increasing evidence suggests that disease phenotypes are strongly related to the virus-induced immune system's dysregulation. Indeed, when the virus-host cross talk is out of control, the occurrence of an aberrant systemic inflammatory reaction, named "cytokine storm," leads to a detrimental impairment of the adaptive immune response. Dendritic cells (DCs) are the most potent antigen-presenting cells able to support innate immune and promote adaptive responses. Besides, DCs play a key role in the anti-viral defense. The aim of this review is to focus on DC involvement in SARS-CoV-2 infection to better understand pathogenesis and clinical behavior of COVID-19 and explore potential implications for immune-based therapy strategies.