Alpha virus vectors engineered for gene delivery and expression of heterologous proteins are valuable tools for research on neurological disorders. They possess a very high efficient susceptibility for neuronal cells and provide extreme levels of heterologous gene expression. However, they generally generate short-term transient expression, which might limit their therapeutic use in many neurological disorders often requiring long-term even life-long presence of therapeutic agents. Recent development in gene silencing applying both RNA interference and micro RNA approaches certainly will expand the application range. Moreover, alpha viruses provide interesting models for neurological diseases such as demyelinating and spinal motor diseases.