Alterations in the genome that lead to changes in DNA sequence copy number are a characteristic of solid tumors and are found in association with developmental abnormalities and/or mental retardation. Comparative genomic hybridization (CGH) can be used to detect and map these changes. Recent improvements in the resolution and sensitivity of CGH have been possible through implementation of microarray-based CGH (array CGH). Here we discuss the performance characteristics of different array platforms and review some of the recent applications of array CGH in cancer and medical genetics.