In the last few decades, intracerebral transplantation has grown from a dubious neuroscientific topic to a plausible modality for treatment of neurological disorders. The possibility for cell replacement opens a new field of perspectives in the therapy of neurodegenerative disorders, ischemia, and neurotrauma, with the most lessons learned from intracerebral transplantation in Parkinson's disease. Multiple animal studies and a few small-scale clinical trials have proven the concept of intracerebral grafting, but still have to provide a uniform and highly efficient approach to the procedure, suitable for clinical application. The success of intracerebral transplantation is highly dependent on the integration of the grafted cells with the host brain. In this process, glial cells are clearly more than passive bystanders. They provide transplanted cells with mechanical support, trophics, mediate synapse formation, and participate in graft vascularization. At the same time, glial cells mediate scarring, graft rejection, and neuroinflammation, which can be detrimental. We can use this information to try to understand the mechanisms behind the glial reaction to intracerebral transplantation. Recognizing and utilizing glial reactivity can move translational research forward and provide an insight not only to post-transplantation events but also to mechanisms of neuronal death and degeneration. Knowledge about glial reactivity to transplanted cells could also be a key for optimization of transplantation protocols, which ultimately should contribute to greater patient benefit.