Retroviral replication has two distinctive features, reverse transcription of the viral ssRNA genome into a dsDNA and integration of the viral DNA into the host genome. Viral DNA integration establishes a provirus in the host genome that resides as a stable viral genetic element for the life of the cell and serves as the source of progeny virion production. However, integration requires the viral preintegration complex (PIC) to overcome the structural barriers of the densely packed chromatin to access the host DNA. Eukaryotic chromosomes are organized by the repeating units of nucleosomes. A nucleosome comprises of a DNA segment of ∼150 base pairs compacted by an octamer of histone proteins, which regulate access to the DNA through a network of chemical modifications. Interestingly, several histone tail modifications play an outsized role in regulating retroviral integration into specific regions of the host genome. Studies in the last few decades have identified several viral and host factors that promote retroviral integration and regulate integration targeting. However, the interaction between the PIC and host nucleosomes that promote retroviral integration is an understudied area. In this review, we will focus on the biochemical and molecular interactions of retroviral PICs with the host nucleosome in an attempt to identify the barriers and factors involved in retroviral integration.