Chromodomain/helicase/DNA-binding domain (CHD) proteins have been identified in a variety of organisms. Despite common features, such as their chromodomain and helicase domain, they have been described as having multiple roles and interacting partners. However, a common theme for the main role of CHD proteins appears to be linked to their ATP-dependent chromatin-remodeling activity. Their actual activity as either repressor or activator, and their cell or gene specificity, is connected to their interacting partner(s). In this minireview, we attempt to match the members of the CHD family with the presence of structural domains, cofactors, and cellular roles in the regulation of gene expression, recombination, genome organization, and chromatin structure, as well as their potential activity in RNA processing.