The present chapter reviews some important approaches in nucleation theory. The classical nucleation theory (CNT) constitutes a versatile tool to explain a vast majority of systems for several decades. However, more recent studies have found that this theory has difficulty applying in the case of protein crystallization and the two-step nucleation theory should be better in the case of the pharmaceutical synthesis process. Thus, understanding of the nucleation process is limited by the resolution of experimental observation techniques. The use of atomic electron tomography to study early-stage nucleation in four dimensions (4D) combined with molecular dynamic simulation results has shown a need to develop a new model beyond the CNT to describe early-stage nucleation at the atomic scale.