Cellular membranes act as signaling platforms and control solute transport. Membrane receptors, transporters and enzymes communicate with intracellular processes via protein-protein interactions. We identified ~12,000 membrane/signaling protein interactions from Arabidopsis, covering a test space of ~6.4x106 pairs using a yeast split-ubiquitin system. While many expected interactions were confirmed, e.g. between heterotrimeric G-protein subunits and between aquaporin isoforms, the vast majority of interactions were unknown previously, including an overrepresented set involving ‘unknowns’. Orthogonal in planta split-GFP assays confirmed >30% of the interactions. Potential regulatory associations in membrane protein trafficking, turnover, and phosphorylation include regulation of a potassium channel by abscisic acid signaling and a brassinolide receptor by trafficking-related proteins. The plant membrane/signaling protein interaction network can serve as a resource for gene discovery and hypothesis generation in all kingdoms.