Angiogenesis is an outgrowth from proliferating blood vessels and acts as an early event in the inflamed joint tissue. It is governed by a tightly controlled balance of pro- and anti-angiogenic stimuli, which promote or inhibit generation and proliferation of new endothelial cells, vascular morphogenesis and vessel remodelling. De novo capillary formation is crucial in maintaining the supply of various nutrients, as well as oxygen to the inflamed tissue. Local and systemic expression of angiogenic factors may indicate a constant remodeling of synovial vasculature. Redox signaling is closely related to angiogenesis and can alter angiogenic responses of synovial cells. In this review, we discuss key issues about endothelial pathology in inflammatory arthritis followed by review of angiogenic processes and main angiogenic mediators within the joint. We review broader aspects of angiogenesis, related systemic inflammation and autoimmune atherosclerosis. We discuss the hypoxia-vascular endothelial growth factor (VEGF)/Ang/Tie2 system and its related therapeutic implications in detail with further review of various mediator protein targets and intracellular regulatory pathway targets with their current and potential future role in preclinical or clinical setting whilst ameliorating inflammation. Our experiments aim to reflect on the detrimental effects of hypoxia and related oxidative stress on aerobic respiration (with a bioenergetic switch towards anaerobic glycolysis in the inflamed synovial tissue and human endothelium) and mitochondrial mutagenesis with their coupled relationship with dysfunctional angiogenesis. In addition, some markers of angiogenesis may readily be measured in the patients’ sera and levels of these markers may correlate with atherosclerosis, vascular pathophysiology and systemic inflammatory activity of arthritides as we will demonstrate below.