Rhabdoid tumors are extremely aggressive malignancies that generally occur in infants and young children. The most common locations are the kidney and central nervous system (atypical teratoid/rhabdoid tumor [RT]), although RTs can also arise in most soft-tissue sites. Rhabdoid tumors in all anatomical locations have a similar molecular origin. Mutation or deletion of both copies of the hSNF5/INI1 gene that maps to chromosome band 22q11.2 is observed in approximately 70% of primary tumors. An additional 20 to 25% of tumors have reduced expression at the RNA or protein level, indicative of a loss-of-function event. The INI1 protein is a component of the SWI/SNF chromatin remodeling complex. The complex is recruited to promoters of a large variety of genes involved in cell signaling, growth, and differentiation. This review summarizes what is currently known regarding the molecular genetics of RTs.