Drug repurposing can be a cost-effective strategy to identify new small molecule-based therapies. Thus, drug repurposing significantly influences the discovery of therapeutics, particularly for rare and neglected diseases, which are often constrained by limited research and development funds. The push for translational science and access to drug discovery-associated resources such as high throughput screening instrumentation, assay development expertise, and Food and Drug Administration-approved drug libraries have intensified interest in drug repurposing. However, successful drug repurposing is highly challenging and subject to particular limitations. Despite these challenges, drug repurposing is a critical component to any comprehensive drug discovery strategy and has the capacity to benefit a wide variety of therapeutically underserved diseases.