As an essential feature of three-dimensional (3D) genome organization, compartmentalization of chromatin in the nucleus is tightly linked to various chromatin activities. Recent work on liquid-liquid phase separation (LLPS), which drives the formation of miscellaneous membrane-less compartments in cells, suggests that it is a critical aspect of chromatin compartmentalization. In this review, we provide an overview of recent work in the animal field that focuses on understanding how LLPS is involved in 3D chromatin organization and transcriptional regulation. By combining scattered information in 3D plant genomics, we attempt to interpret some known plant chromatin organization patterns in the context of LLPS. Moreover, we discuss and speculate factors that can undergo phase separation to modulate chromatin structure and gene expression in plants.