Soybean mosaic virus (SMV) occurs in all soybean-growing areas in the world and causes huge losses in soybean yields and seed quality. During early viral infection, molecular interactions between SMV effector proteins and the soybean resistance (R) protein, if present, determine the development of resistance/disease in soybean plants. Depending on the interacting strain and cultivar, R-protein in resistant soybean perceives a specific SMV effector, which triggers either the extreme silent resistance or the typical resistance manifested by hypersensitive responses and induction of salicylic acid and reactive oxygen species. In this review, we consider the major advances that have been made in understanding the soybean–SMV arms race. We also focus on dissecting mechanisms SMV employs to establish infection and how soybean perceives and then responds to SMV attack. In addition, progress on soybean R-genes studies, as well as those addressing independent resistance genes, are also addressed.