Plant viruses are responsible for losses in worldwide production of numerous economically important food and fuel crops. As obligate cellular parasites with very small genomes, viruses rely on their hosts for replication, assembly, intra- and intercellular movement, and attraction of vectors for dispersal. Chloroplasts are photosynthesis and are the site of replication for several viruses. When viruses replicate in chloroplasts, photosynthesis, an essential process in plant physiology, is inhibited. The mechanisms underlying molecular and biochemical changes during compatible and incompatible plants–virus interactions, are only beginning to be elucidated, including changes in proteomic profiles induced by virus infections. In this review, we highlight the importance of proteomic studies to understand plant–virus interactions, especially emphasizing the changes in photosynthesis-related protein accumulation. We focus on: (a) chloroplast proteins that differentially accumulate during viral infection; (b) the significance with respect to chloroplast-virus interaction; and (c) alterations in plant’s energetic metabolism and the subsequently the plant defense mechanisms to overcome viral infection.