Multicellularity differs in plants and animals in that the cytoplasm, plasma membrane, and endomembrane of plants are connected between cells through plasmodesmal pores. Plasmodesmata (PDs) are essential for plant life and serve as conduits for the transport of proteins, small RNAs, hormones, and metabolites during developmental and defense signaling. They are also the only pathways available for viruses to spread within plant hosts. The membrane organization of PDs is unique, characterized by the close apposition of the endoplasmic reticulum and the plasma membrane and spoke-like filamentous structures linking the two membranes, which define PDs as membrane contact sites (MCSs). This specialized membrane arrangement is likely critical for PD function. Here, we review how PDs govern developmental and defensive signaling in plants, compare them with other types of MCSs, and discuss in detail the potential functional significance of the MCS nature of PDs.