Genetic risk factors that underlie many rare and common neurological disorders remain poorly understood because of the multifactorial and heterogeneous nature of these complex traits. With the decreasing cost of massively parallel sequencing technologies, whole-genome and whole-exome sequencing will soon allow the characterization of the full spectrum of sequence and structural variants present in each individual. Methods are being developed to parse the huge amount of genomic data and to sift out which variants are associated with diseases. Numerous challenges are inherent in the identification of rare and common variants that have a role in complex neurological diseases, and tools are being developed to overcome these challenges. Given that genomic data will soon be the main driver towards the goal of personalized medicine, future developments in the production and interpretation of data, as well as in ethics and counselling, will be needed for whole-genome and whole-exome sequencing to be used as informative tools in a clinical setting.