Heterodera glycines (i.e., soybean cyst nematode, SCN) is the most damaging nematode pest affecting soybean crop worldwide. This nematode is managed by means of crop rotation with selected resistant sources. With increasing reports of virulent SCN populations that are able to break the resistance within commonly used sources, there is an increasing need to find new sources of resistance or to broaden the resistance background. This review summarizes recent findings about the genes controlling SCN resistance in soybean, and about how these genes interact to confer resistance against SCN in soybean. It also provides an update on molecular mapping and molecular markers that can be used for the mass selection and differentiation of different resistance lines and cultivars in order to expedite conventional breeding programs. In-depth knowledge of SCN parasitism proteins and soybean resistance responses to the pathogen is critical for the diversification of resistant sources through gene modification, gene stacking, or incorporation of novel sources of resistance through backcrossing or genetic engineering.