Abstract: The goal of cell division is to segregate genetic material, in the form of chromosomes, equally into the two daughter cells. To achieve this goal, each chromosome must physically connect with the two poles of the mitotic spindle, a macromolecular machine responsible for delivering the two molecules of DNA within the chromosome (i.e., 'chromatids') to the opposite poles. Research in my laboratory aims to reveal the mechanism(s) that allow these connections to form rapidly yet with minimal number of errors. Most recently we used a combination of live-cell recordings, correlative 3D light/electron microscopy, and computational modeling to analyze behavior of chromosomes in human cells under various experimental conditions. Based on these investigations, we formulate a novel model for mitotic spindle assembly. In contrast to the conventional view that various chromosomes within a cell connect to the spindle poles at random, our model envisions formation of these connections as a deterministic process in which connections to the poles appear synchronously on multiple chromosomes. This happens at a specific stage of spindle assembly and at a defined location determined by the spindle architecture. Experimental analyses of changes in the kinetochore behavior in cells with perturbed activity of molecular motors CenpE and dynein confirm the predictive power of the model.