Central nervous system disorders remain the leading causes of mortality and morbidity worldwide, affecting more than 1 billion patients. This therapeutic area suffers from high unmet medical needs and the search for innovative approaches to identify therapeutic strategies is urgent in the field. This review will first cover the challenges and opportunities of drug discovery in neurology, and then as well as the new models, such as human model stem cells and animal models under development in the field. In addition, innovative and translational neuroimaging techniques will be discussed, as the use of big data and artificial intelligence to discovery new drugs in neurological and neuropsychiatric disorders.