Objectives of the present work are as follows: • To study the current principles of rare diseases & orphan drugs. • To study the assessment, challenges and regulatory frame work of orphan drugs • To study the integrated approach for the development and approval of orphan drugs. • To carry out the study of globalization in orphan drug development strategies in US & EU markets. Methods: Internet using web page content: The literature was collected using numerous search engines e.g. Science Direct, Google Scholar and many more. Online books also served as a good source of information. Documents and information’s collected using numerous regulatory websites such as: a) USFDA: https://www.fda.gov b) EMA: https://www.ema.europa.eu/en c) CANADA: https://www.canada.ca/en/health-canada.html d) TGA: https://www.tga.gov.au/ e) INDIA: http://www.cdsco.com/ Results: US- FDA Approved Orphan Drug ex: Tafenoquine - Treatment of malaria - Krintafel is indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria. EU – EMA Approved Orphan Drug ex: Eculizumab, Soliris - Treatment myasthenia gravis. Conclusion: The orphan drug guidelines made via distinct countries have established as promoters in development of orphan drugs. The orphan drug regulation in the US and the EU has been a success in offering remedies to the patients with rare diseases.