RNA silencing, including gene quelling in fungi and RNA interference in animals, refers to a process of homologous, sequence-specific, RNA-based, post-transcriptional gene silencing triggered by double- stranded RNA that requires a conserved set of gene products. RNA-induced, homology-dependent gene silencing can also spread locally and systemically between cells to orchestrate developmental programs in plants. The mobile RNAi signal could consist of a complex of small RNAs and proteins. In plants, the mobile RNAi signals may traffic beyond sites of initiation through plasmodesmata channels (cell-to-cell movement) and also over long distances through the phloem (systemic movement). Small interfering RNA processed by DICER-like proteins is considered a hallmark of RNAi mobility, and the phloem represents a unique highway for long-distance spreading of RNAi signals. To date, molecular and genetic studies have identified a few RNA molecules and protein components that function in silencing spread mechanisms. However, the processes involved in cell-to-cell movement of RNAi signals remain poorly understood. To gain further insight into noncell- autonomous RNAi spreading networks, it is critical to discover and characterize the distinct functions of the various genetic and molecular components involved. In this review, we discuss current advances, as well as gaps, in our understanding of cell-to-cell RNAi spread pathways and their implications for fundamental biology in plants.