Six Sigma, as indicated by its name, requires any process or product to reduce its error or defect into 3.4 defects per million opportunities . Six sigma methodologies is initiated by Motorola and made popular by General Electric Company . Sig Sigma helps the organization to reduce the cost of operation, reduce waste or errors or defects, increase the customer satisfaction and increase employee engagement. Six Sigma is not only confined to quantitative aspect but includes many other quality related process such as management commitment, continuous training, inculcation of quality culture in the organization etc. This paper provides an overview of Six Sigma methodology, its usefulness in Biomedical Domain, its process and tools used in the Six Sigma process.