Intracellular signaling from plastids to the nucleus, called retrograde signaling, coordinates the expression of nuclear and plastid genes and is essential for plastid biogenesis and for maintaining plastid function at optimal levels. Recent identification of several components involved in plastid retrograde generation, transmission, and control of nuclear gene expression has provided significant insight into the regulatory network of plastid retrograde signaling. Here, we review the current knowledge of multiple plastid retrograde signaling pathways, which are derived from distinct sources, and of possible plastid signaling molecules. We describe the retrograde signaling–dependent regulation of nuclear gene expression, which involves multilayered transcriptional control, as well as the transcription factors involved. We also summarize recent advances in the identification of key components mediating signal transduction from plastids to the nucleus.