Large-scale genomics projects such as the Human Genome Project and the International HapMap Project promise significant advances in the ability to diagnose and treat many conditions, including those with a neurological basis. A major focus of research has emerged in the neurological sciences to elucidate the molecular and genetic basis of various neurological diseases. Indeed, genetic factors are implicated in susceptibility for many neurological disorders, with family history studies providing strong evidence of familial risk for conditions such as stroke, Parkinson's, Alzheimer's, and Huntington's diseases. Heritability studies also suggest a strong genetic contribution to the risk for neurological diseases. Genome-wide association studies are also uncovering novel genetic variants associated with neurological disorders. Whole-genome and exome sequencing are likely to provide novel insights into the genetic basis of neurological disorders. Genetic factors are similarly associated with clinical phenotypes such as symptom severity and progression as well as response to treatment. Specifically, disease progression and functional restoration depend, in part, on the capacity for neural plasticity within residual neural tissues. Furthermore, such plasticity may be influenced in part by the presence of polymorphisms in several genes known to orchestrate neural plasticity including brain-derived neurotrophic factor (BDNF) and Apolipoprotein E. (APOE). It is important for neurorehabilitation therapist practicing in the “genomic era” to be aware of the potential influence of genetic factors during clinical encounters, as advances in molecular sciences are revealing information of critical relevance to the clinical rehabilitation management of individuals with neurological conditions. Video Abstract available (See Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A88) for more insights from the authors.