Proteomics is a useful analytical approach for investigating crop responses to stress. Recent remarkable advances in proteomic techniques allow for the identification of a wider range of proteins than was previously possible. The application of proteomic techniques to clarify the molecular mechanisms underlying crop responses to flooding stress may facilitate the development of flood tolerant crops. Flooding is an environmental stress found worldwide and may increase in frequency due to changes in global climate. Waterlogging resulting from flooding causes significant reductions in the growth and yield of several crops. Transient flooding displaces gases in soil pores and often causes hypoxia in plants grown on land with poor drainage. Changes in protein expression and post-translational modification of proteins occur as plants activate their defense system in response to flooding stress. In this review, we discuss the contributions that proteomic studies have made toward increasing our understanding of the well-organized cellular response to flooding in soybean and other crops. The biological relevance of the proteins identified using proteomic techniques in regard to crop stress tolerance will be discussed as well.