Stem cells are believed to provide a tool by which new cells and tissues can be made and by which damaged ones can be replaced or repaired. Besides the enormous impact in the cell replacement field, and in particular for the central nervous system (CNS) since cell transplantation might help to overcome the intrinsic poor capability of the nervous tissue to replace elements lost in the course of injury or disease, the stem cell technology is becoming particularly important for others applications. Indeed, with a recent growing awareness of how stem cells can be made to grow in an unlimited, but regulated manner and how their fate can be directed or manipulated into mature phenotypes in culture, it has become clear that the biological resource offers additional attractive features applicable for future biomedical research. While it is also anticipated that stem cells of human origin will provide reagents that will revolutionise aspects of biomedical and pharmacological fields, in the last few years, stem cells have been proved a valuable tool for modelling diseases and studying signalling mechanisms in order to obtain optimized drugs. Here, data will be presented about the employment of ES cells and Neural Stem cells for: 1) the investigation of signalling commitments from the Shc family of signal transduction molecules during the induction, the proliferation and neuronal differentiation events in the developing brain 2) the generation of optimized cellular systems for the study of the molecular mechanisms underlying neurologic disease, and in particular Huntington’s disease