T. cruzi undergoes distinct developmental programs during its replication cycle and during its lifecycle where it shuttles between mammal and triatomine hosts. The information required to achieve these complex morphological and biochemical changes is encoded in the genome at several different levels. A preliminary understanding of the biochemical, physiological, and morphological changes that occur in the different lifestages of T. cruzi requires a detailed knowledge of the parasites genome composition and function. Here, we review the role of the nucleus in parasite identity. We begin with an analysis of how gene organization is resolved by mechanisms of mRNA formation, and the inherent signals in mRNAs that enable stage-specific protein expression. We continue with a description of the genome of the CL Brener strain as determined by the T. cruzi genome-sequencing project, including analysis of repetitive elements, structural genes, and some protein-coding genes. We end with a discussion of T. cruzi population structure and the discovery of rare nuclear hybridization events.