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Osteoarthritis (OA) is the major cause of disability, affecting over 30 million US adults. Continued research into the role of neovascularization and inflammation related to osteoarthritis in large-animal models and human clinical trials is paramount. Recent literature on the pathogenetic model of OA has refocused on low-level inflammation, resulting in joint remodeling. As a result, this has redirected osteoarthritis research toward limiting or treating joint changes associated with persistent synovitis. The overall goal of this review is to better understand the cellular and tissue-specific mechanisms of inflammation in relation to a novel OA treatment modality, Genicular Artery Embolization (GAE). This article also assesses the utility and mechanism of periarticular neovascular embolization for the treatment of OA with a particular emphasis on the balance between pro-angiogenic and anti-angiogenic cytokines, inflammatory biomarkers, and imaging changes.