In this chapter, we review the structure and composition of interphase and mitotic chromosomes. We discuss how these observations support the model that mitotic condensation is a deterministic process leading to the invariant folding of a given chromosome. The structural studies have also placed constraints on the mechanism of condensation and defined several activities needed to mediate condensation. In the context of these activities and structural information, we present our current understanding of the role of cis sites, histones, topoisomerase II, and SMC proteins in condensation. We conclude by using our current knowledge of mitotic condensation to address the differences in chromosome condensation observed from bacteria to humans and to explore the relevance of this process to other processes such as gene expression.