Cellular processes are dictated by the active signaling of proteins relaying messages to regulate cell proliferation, apoptosis, signal transduction and cell communications. An intricate web of protein kinases and phosphatases are critical to the proper transmission of signals across such cascades. By governing 30-50% of all protein dephosphorylation in the cell, with prominent substrate proteins being key regulators of signaling cascades, the phosphatase PP2A has emerged as a celebrated player in various developmental and tumorigenic pathways, thereby posing as an attractive target for therapeutic intervention in various pathologies wherein its activity is deregulated. This review is mainly focused on refreshing our understanding of the structural and functional complexity that cocoons the PP2A phosphatase, and its expression in cancers. Additionally, we focus on its physiological regulation as well as into recent advents and strategies that have shown promise in countering the deregulation of the phosphatase through its targeted reactivation. Finally, we dwell upon one of the key regulators of PP2A in cancer cells-cellular redox status-its multifarious nature, and its integration into the reactome of PP2A, highlighting some of the significant impacts that ROS can inflict on the structural modifications and functional aspect of PP2A.