Background <p>Drug repurposing describes the approval of an already authorized medicine for a new therapeutic indication. Rising development costs, long clinical timelines and attrition in first-in-class discovery have renewed interest in this strategy as a way to extend pharmacological value using pre-validated mechanisms. This study evaluates how repurposing has contributed to pharmaceutical innovation over four decades, examining approval patterns, therapeutic redirection and industry behavior.</p> Methods <p>A longitudinal dataset of all new molecular entities and biologic products approved by the United States regulator between 1985 and 2024 was constructed. Repurposing was defined strictly as a new therapeutic indication distinct from the original approval. All cases were verified using regulatory documentation. Descriptive analyses quantified approval volumes, therapeutic transitions, applicant trajectories and development intervals. We compared the time to repurposing when development remained within the original company versus when rights transferred externally.</p> Results <p>Here we show that 451 drugs received subsequent approval for a new therapeutic use, representing a substantial fraction of authorized medicines. Oncology and neurological disorders act as major nodes of redirection, serving both as frequent endpoints and as mechanistic sources for cross-domain translation. The mean interval between first approval and repurposing is 7.2 years, shorter than typical development timelines for newly originated drugs. Repurposing occurs more rapidly when development rights remain with the original owner, and large firms account for most approvals.</p> Conclusions <p>Repurposing has become a durable component of pharmaceutical innovation, enabling faster clinical deployment of validated mechanisms across disease domains. These findings highlight its potential to expand treatment options while reducing R&amp;D uncertainty.</p>