The outcome of synthetic procedures for crystalline organic materials strongly depends on the first steps along the molecular self-assembly pathway, a process we know as crystal nucleation. New experimental techniques and computational methodologies have spurred significant interest in understanding the detailed molecular mechanisms by which nuclei form and develop into macroscopic crystals. Although classical nucleation theory (CNT) has served well in describing the kinetics of the processes involved, new proposed nucleation mechanisms are additionally concerned with the evolution of structure and the competing nature of crystallization in polymorphic systems. In this Review, we explore the extent to which CNT and nucleation rate measurements can yield molecular-scale information on this process and summarize current knowledge relating to molecular self-assembly in nucleating systems. Everything starts out small: The synthesis of organic materials depends strongly on the first steps of molecular self-assembly during crystal nucleation. This Review summarizes current knowledge on these processes. Self-association in different solvents can lead to the creation of different building blocks, which form differently packed nuclei and thus in each case specific crystalline phases. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.