Co-operation of the endogenous and exogenous defense system maintains redox homeostasis and is essential for health. The endogenous defense system includes enzymatic (e.g. superoxide dismutase, catalase) and non-enzymatic, low molecular-weight scavengers (e.g. glutathione, ascorbic acid). Pathogenesis of many serious diseases (e.g. cancer, ischemic heart disease) includes oxidative stress which can disturb angiogenesis, the process of formation of new blood vessels sprouting from the existing one. Antioxidants, through reduction of oxidative stress and influence on neovascularization, may modulate progress and results of therapy in those diseases where such processes play an important role. Herein the impact of exogenous antioxidants on angiogenesis and factors modulating this process is presented. Most synthetic antioxidants whose activity has been described (namely N-acetylcysteine, pentoxifylline, synthetic analogue of curcumin, synthetic analogue of epigallocatechin-3 gallate [EGCG], tripertenoids) exert an inhibitory effect on neovascularization. A similar effect was also exhibited by several natural origin antioxidants (e.g. resveratrol, EGCG), which suggests that their application in therapy might normalize excessive angiogenesis. Some natural origin antioxidants e.g. purple coneflower and preparations consisting of natural antioxidants such as Padma 28 and Immunal forte increase a too low baseline level of angiogenesis and decreases a too high level. These preparations exert a regulatory effect on and may normalize neovascularization. They can be used in the case of diseases associated with too low or too high angiogenesis.