The development of “omic” technologies and deep phenotyping may facilitate a systems biology approach to understanding anxiety disorders. Systems biology approaches incorporate data from multiple modalities (e.g., genomic, neuroimaging) with functional analyses (e.g., animal and tissue culture models) and mathematical modeling (e.g., machine learning) to investigate pathological biophysical networks at various scales. Here we review: i) the neurobiology of anxiety disorders; ii) how systems biology approaches have advanced this work; and iii) the clinical implications and future directions of this research. Systems biology approaches have provided an improved functional understanding of candidate biomarkers and have suggested future potential for refining the diagnosis, prognosis, and treatment of anxiety disorders. The systems biology approach for anxiety disorders is, however, in its infancy and in some instances is characterized by insufficient power and replication. The studies reviewed here represent important steps to further untangling the pathophysiology of anxiety disorders.