Plants integrate a variety of biotic and abiotic factors for optimal growth in their given environment. While some of these responses are local, others occur distally. Hence, communication of signals perceived in one organ to a second, distal part of the plant and the coordinated developmental response require an intricate signaling system. To do so, plants developed a bipartite vascular system that mediates the uptake of water, minerals, and nutrients from the soil; transports high-energy compounds and building blocks; and traffics essential developmental and stress signals. One component of the plant vasculature is the phloem. The development of highly sensitive mass spectrometry and molecular methods in the last decades has enabled us to explore the full complexity of the phloem content. As a result, our view of the phloem has evolved from a simple transport path of photoassimilates to a major highway for pathogens, hormones, and developmental signals. Understanding phloem transport is essential to comprehend the coordination of environmental inputs with plant development and, thus, ensure food security. This review discusses recent developments in its role in long-distance signaling and highlights the role of some of the signaling molecules. What emerges is an image of signaling paths that do not involve single molecules but rather, quite frequently an interplay of several distinct molecular classes, many of which appear to be transported and acting in concert.