The aim of this project was to investigate the molecular mechanisms of shade-avoidance response in tomato (Solanum lycopersicum) plants. Plants were grown in direct sunlight in ambient temperature and in an adjacent environment under shade cloth. Leaves were harvested, and protein expression differences were investigated using two-dimensional differential in-gel electrophoresis and nanoflow high-performance liquid chromatography–tandem mass spectrometry. Striking differences in plant physiology and protein expression were observed. Plants grown in the shade grew very tall but bore almost no fruit and displayed a dramatic reduction in the accumulation of Rubisco and a number of other metabolic enzymes. We have identified, quantified, and classified 59 protein features found to be up- or down-regulated as part of a shade-avoidance response in S. lycopersicum and correlated these with phenotypic data. A large group of proteins related to metabolism and respiration were greatly reduced in accumulation in shade-grown plants, and there was also evidence of significant proteolysis occurring. Four stress-related proteins appear to be constitutively expressed as a result of heat acclimation, while three distinct stress-related proteins appear to accumulate as part of the shade-avoidance response. The identification and functional classification of all 59 differentially accumulating proteins is presented and discussed.