ntroduction: Cell encapsulation technology has improved enormously since it was proposed 50 years ago. The advantages offered over other alternative systems, such as the prevention of repetitive drug administration, have triggered the use of this technology in multiple therapeutic applications. Areas covered: In this article, improvements in cell encapsulation technology and strategies to overcome the drawbacks that prevent its use in the clinic have been summarized and discussed. Different studies and clinical trials that have been performed in several therapeutic applications have also been described. Expert opinion: The authors believe that the future translation of this technology from bench to bedside requires the optimization of diverse aspects: i) biosafety, controlling and monitoring cell viability; ii) biocompatibility, reducing pericapsular fibrotic growth and hypoxia suffered by the graft; iii) control over drug delivery; iv) and the final scale up. On the other hand, an area that deserves more attention is the cryopreservation of encapsulated cells as this will facilitate the arrival of these biosystems to the clinic.