The Ikzf1 gene encodes Ikaros-a DNA-binding zinc finger protein. Ikaros functions as a regulator of gene expression and chromatin remodeling. The biological roles of Ikaros include regulating the development and function of the immune system and acting as a master regulator of hematopoietic differentiation. Genomic profiling studies identified Ikzf1 as an important tumor suppressor in acute lymphoblastic leukemia (ALL), particularly in ALL that is associated with poor prognosis. This review summarizes currently available data regarding the structure and function of Ikaros, the clinical relevance of genetic inactivation of Ikzf1, and signal transduction pathways that regulate Ikaros function.