Eukaryotic chromosomes have many challenges to overcome between DNA replication and sister chromatid segregation. If these challenges are not met, cell death or unregulated cell division (cancer) may result. During prophase, chromosomes condense, the nuclear membrane breaks down and cohesins are removed from chromosome arms. In prometaphase, initial spindle attachments are made by sister kinetochores followed by correction of erroneous attachments, centromere oscillation between spindle poles and congression towards the cell's equator. In metaphase, all chromosomes attain stable bipolar spindle attachments and align at the metaphase plate, ready for the metaphase-anaphase transition when all ties between sister chromatids are broken. This review concentrates on recent developments that have revealed the intricacies of these processes. We now know more about how the mechanisms of cohesin removal differ between prophase and the metaphase-anaphase transition, the processes for detection and correction of improper spindle-kinetochore attachments and the concept that tension between sister kinetochores is the driving factor for satisfying the spindle checkpoint. We are also beginning to gain some understanding of the mechanisms behind the co-segregation of sister chromatids at the first meiotic division.