Although disordered chromatin organization has long been recognized as a feature of cancer, the molecular underpinnings of chromatin structure, epigenetic regulation, and their relationships to transcription are only beginning to be understood. Cancer genome sequencing studies have revealed a novel theme: frequent mutation of epigenetic regulators. Among these, the ARID1A/BAF250A subunit of the SWI/SNF (BRG1-associated factors) chromatin remodeling complex has emerged as recurrently mutated in a broad array of tumor types. We review the genomic and functional data supporting classification of ARID1A as a tumor suppressor. Mutations in chromatin remodeling complex genes are increasingly recognized in many cancer types. However, the mechanisms by which chromatin remodeling complexes contribute to gene expression and the cancer phenotype are poorly understood. Understanding how mutation of chromatin remodelers facilitates transformation may offer the potential for development and implementation of novel therapies for cancer.