Background: Restoration of eyelid and lacrimal functions are important steps on the way to an intact ocular surface. Clinically available substitute tissues or therapeutic options for eyelid reconstruction and lacrimal gland regeneration often reach their limits in patients with severe diseases of the adnexa oculi. Several approaches in regenerative medicine have been intensively researched and clinically tested in recent years. These range from reconstructive approaches with novel tissue matrices in the field of eyelid surgery to stem cell therapies to regenerate lacrimal gland function. Material and methods: The state of the art in the current literature is presented and an overview of clinically applied or currently researched tissues for eyelid reconstruction is given. Furthermore, approaches in stem cell therapy of the lacrimal gland as well as own results are presented. Results: Acellular dermis has been successfully used for eyelid reconstruction and represents a viable option in cases of limited availability of autologous tissue. In vitro grown cellular constructs or tissues with genetically modified cells have already been successfully applied in dermatology for the treatment of burns or severe genodermatoses. First studies on stem cell therapy for severe dry eye in Sjögren syndrome showed a safe and effective application of mesenchymal stem cells by injection into the lacrimal gland. Conclusion: Due to the limitations of currently available replacement tissues, there is a clinical need for the development of new materials for adnexa oculi reconstruction. Constructs grown in vitro with allogeneic and/or genetically engineered cells are slowly making their way into clinical practice. The efficacy and mode of action of stem cells in severe dry eye are subject matters of current clinical trials.