Rare diseases are a group of unusual pathologies suffering millions of people worldwide. To date, about 6000–8000 rare diseases have been recorded. Due to high expenses and a lack of profitability associated with drug development, new treatments for these conditions are often limited. Over the past several decades, orphan drugs have played an increasingly important role in the treatment of rare diseases. Even so, the development of these therapies remains challenging, and there are currently no approved treatments for many rare diseases. The development of a de novo drug is a process that requires a considerable amount of prior research, and pharmaceutical companies spend millions of dollars annually to carry out this task. An average of 10–17 years is expected to be spent on this process and the cost is estimated to be between $2–3 billion. Therefore, drug repurposing has emerged as a viable strategy for identifying potential new treatments for these pathologies, a technique that consists of using existing drugs to treat a new disease different from the one that they were developed for. As a result, drug development time and cost can be reduced significantly while the likelihood of success increases. This chapter aims to compile the relevant discoveries in recent years that address the problem related to the lack of treatments for rare diseases and the fundamental role played by orphan drugs and drug repurposing in this domain.