Chromosome damage is a critical indicator of genetic damage relevant to environmental and clinical studies. Detailed descriptions of the protocols used for the detection of chromosomal aberrations induced by genotoxic agents in vitro in both the presence and absence of rat liver-derived metabolizing systems are given in this chapter. Structural chromosomal aberrations that can be observed and quantified at metaphases are described here. For the detection of chromosomal damage (fragments or whole chromosome) in interphase, the micronucleus test can be used and a description of this test is also presented. Criteria for determining a positive result using appropriate statistical methods are also described.