Quality management system implementation in clinical laboratories is becoming mandatory. A reasonable easy to practice approach is a key element for success. Clinical and Laboratory Standards Institute (CLSI) QMS01-A4 has provided a detailed practical approach that focuses on twelve main items; named quality essentials. Incorporating these essentials in daily practice in the microbiology laboratory mandates creating an environment that practices ‘quality' by default. This review provides a step-by-step approach to facilitate the implementation of the twelve essentials of the CLSI QMS while keeping an eye on the ISO 15189 requirements. The twelve quality essentials delineated namely are: Organization, Customer focus, Facilities and Safety Management, Personnel Management, Purchasing and Inventory Management, Equipment, Process Management, Documents and Records, Information Management, Nonconforming events Management, Assessments and Continual Improvement. These essentials are designed to cover the whole testing process. Whenever applicable, real-life examples from the daily practice are added to make the picture clearer.