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The Polycomb repressive system is a conserved, chromatin-based transcriptional regulator that is essential for the normal development of multicellular organisms. Polycomb-group proteins catalyze repressive histone modifications and organize 3D chromatin interactions. While the relationship between Polycomb-deposited histone modifications and gene repression is well-established, how Polycomb-mediated 3D chromatin interactions contribute to gene regulation remains poorly understood. In this review, we discuss current insights into the formation of these interactions and potential models for how they contribute to Polycomb-dependent gene regulation.