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This study aimed to review the requirements and difficulties of natural and artificial regeneration of cork oak (Quercus suber L.) in the Mediterranean Basin. Cork oak regeneration is achieved naturally by means of sexual or vegetative reproduction (by seeds or by sprouting), or artificially through direct seeding, or seedling planting. Both natural and artificial regeneration of cork oak frequently encounter numerous difficulties which limit the ecological conditions for cork oak regeneration, including acorn predation, slow growth, vegetative competition, browsing of seedlings, fires, pests and diseases, and summer drought. We reviewed the state of the art of these difficulties and summarize the potential solutions for each regeneration form.