Neurodegenerative diseases are a heterogenous group of neurological diseases characterized by a progressive loss of more or less specific neuronal and glial populations. Despite the major improvements of these last 3 decades in the understanding of their pathogenesis, their therapy is still problematic and, in most cases, not sufficiently effective. Particularly, for most of the neurodegenerative diseases, there is a lack of causal therapies that would rescue degenerating neurons or glial cells. The aim of this chapter is to describe the process of development and testing new therapies for neurodegenerative diseases and discuss its pitfalls. Although the emphasis is on pharmacotherapy, analogous principles are applicable on development of other therapeutic approaches. The role and importance of preclinical models in this translational research is highlighted.