In this chapter, we first discuss the structural and functional aspects of human chromosomes. The human genome is packaged into a set of chromosomes, which are derived in equal numbers from the mother and the father. Each ovum and sperm contains a set of 23 different chromosomes, which is the haploid number of chromosomes in humans. The diploid fertilized egg and virtually every cell of the body arising from it has two haploid sets of chromosomes, resulting in the diploid human chromosome number of 46. The haploid human genome consists of approximately 3 × 109 bp of DNA. This DNA is compacted in a hierarchy of levels into chromosomes of manageable size. We then discuss the two types of cell division, namely mitosis and meiosis. In somatic cells, nuclear division takes place by mitosis. During mitosis each chromosome divides into two daughter chromosomes, one of which segregates into each daughter cell, thus producing daughter cells with identical chromosome constitutions. Meiosis, however, is a specialized cell division in germ cells that generates gametes with the haploid set of 23 chromosomes. The final gametic set includes single representatives of each of the 23 chromosome pairs selected at random. Next, we discuss the methods used to study human chromosomes, including both conventional chromosome banding and molecular cytogenetic techniques. We then touch on the concept of genomic imprinting and its role in human genetic disease. Finally, we briefly review the various types of human chromosomal abnormalities.