Abstract Accurate chromosome segregation during both mitosis and meiosis is governed by an intricate and synchronised cascade of events. These are controlled by the molecular networks that ensure the proper assembly of sister deoxyribonucleic acid (DNA) molecules produced during DNA replication, followed by the action of the spindle that pulls the sister chromatids apart. Mistakes in these processes would lead to chromosome transmission defects and subsequent aneuploidy, a common hallmark of many tumour cells. Herein, we review recent progresses in the molecular illustration of the chromosome architecture and function specially those depending on the structural maintenance of chromosome family of protein complexes, in conjunction with the spatio‐temporal regulation of cell‐cycle progression. Key Concepts: Cohesin is the glue that entraps duplicated sister DNA. DNA replication is coupled to the establishment of sister‐chromatid cohesion through cohesin acetylation. The bulk of cohesin is removed from chromosome arms by phosphorylation in early stages of mitosis, whereas centromeric cohesin is removed by separase‐mediated cleavage at the metaphase anaphase transition. Condensin is required for a proper mitotic chromosome assembly. Smc family of protein complex determine chromosomal structure and function throughout the cell cycle. Separase is tightly regulated in cell cycle and become active exclusively at the onset anaphase. SAC monitors the presence of unattached kinetochores. Protein degradation mediated by the APC/C drives anaphase onset. Back‐to‐back orientation of kinetochores is required for Meiosis II and mitosis, whereas, side‐by‐side orientation of kinetochores is required for meiosis I. Shugoshin protects precocious dissociation of cehesin. Bi‐orientation of chromosomes depends on the correction mechanisms and spindle assembly checkpoint.