Background: A pharmacological agent known as an orphan drug was created to address rare or orphan diseases. The Food and Drug Administration (FDA) claims that the Orphan Drug Act has certainly encouraged the development of treatments for rare diseases. The Orphan Drug Act was passed in the United States in 1983 to encourage pharmaceutical companies to develop treatments for rare diseases. Global sales of orphan drugs are anticipated to increase at a Compound Annual Growth Rate (CAGR) of 12.3% from 2019 to 2024, which is roughly double the rate anticipated for the non-orphan drug industry. India has between 72 and 96 million people who are affected by rare diseases. There are no specific orphan drug laws in India. The Ministry of Health and Family Welfare of India established a National Policy for the Treatment of Rare Diseases in July 2017 (NPTRD). However, there were challenges to the execution of the policy. The Orphan Drug Act, which was passed on January 4, 1983, gave orphan medications legal status in the United States. The lack of orphan drug regulation hurts the Indian pharmaceutical businesses' ability to thrive economically. Contrarily, the US's orphan drug regulations have been effective in bringing therapies to people with rare disorders. The assessment of the scope and impact of orphan diseases, as well as a widespread awareness campaign about orphan diseases, are urgently needed in the current situation. Orphan drug development requires strong policies and initiatives from both public and private institutions. Materials and Methods: This review article is based on the information collected from various sources from FDA and NPTRD and the articles mentioned. Results: The different guidelines and regulations for the development and manufacture of orphan pharmaceuticals should be put into place to ensure that orphan diseases get the necessary treatment and care. Conclusion: The FDA regularly updates and the Orphan Drug Act provides direction for the overall rules and regulations in the United States. In India, being a semi-regulated market, there are no such specific rules and regulations regarding development. The National Policy for Rare Disease in India 2021 helps as a guidance document regarding the policies related to orphan drugs in India.