Protein-protein interactions are essential for nearly all cellular processes. Therefore, an important goal of post-genomic research for defining gene function and understanding the function of macromolecular complexes involves creating 'interactome' maps from empirical or inferred datasets. Systematic efforts to conduct high-throughput surveys of protein-protein interactions in plants are needed to chart the complex and dynamic interaction networks that occur throughout plant development. However, no single approach can build a complete map of the interactome. Here, we review the utility and potential of various experimental approaches for creating large-scale protein-protein interaction maps in plants. Bioinformatics approaches for curating and assessing the confidence of these datasets through inter-species comparisons will be crucial in achieving a complete understanding of protein interaction networks in plants.