The chromatin remodeling complexes alter chromatin structures. They remodel nucleosomes in ATP-dependent manner and have essential roles in DNA damage repair, recombination, replication and transcriptional control. Increasing evidences indicate that subunits of chromatin remodelers are mutated and/or deregulated in a number of human cancers, and how they influence the cancer gene expression program during cancer initiation and progression is becomming clearer. Therefore, chromatin remodeling complexes arose as promising new targets for the treatment of human cancers. In this review, chromatin remodeling complexes, their epigenetic reader domains and available inhibitors are described. The insights into the misregulated chromatin remodelers pathways in human malignancies and the novel approach targeting deregulated chromatin remodelers to improve chemotherapy efficiency are discussed.