For both the investigation of etiopathogenesis and the discovery of novel therapies in neurodegenerative diseases, many types of preclinical models are used. The main classification is into 3 categories: in vivo, in vitro and in silico. These types have many subtypes and can be categorized also according to other aspects. This chapter highlights importance of preclinical models in biomedical research, provides an overview of model types, discusses advantages and limitations and underlines principles of their generation from the general point of view referring in details to specialized chapters. Principles of modeling diseases and syndromes and importance of model construct, face and predictive validity for translational research are discussed.