Abstract Background: In recent decades, dramatic changes have occurred in the organization, number and type of tests, and role of medical laboratories in healthcare. The role of laboratory professionals has undergone a radical change, which calls for greater analytical accuracy, and more stringent test selection, and interpretation of results. Methods: The ancillary role of clinical laboratories in the past was analyzed in order to understand why the change has taken place, and to identify old and new areas in which laboratory information is largely used for improving upon decision making for treatment, and patient management. Results: The availability of real-time laboratory results and more effective tests, the enhanced clinical consulting role, the involvement in therapeutic decisions, the efforts to prevent rather than cure disease, the shift from anecdotal care to evidence-based medicine, and the assessment of outcome for laboratory tests have all contributed to the changing role and duties of medical laboratories. Conclusions: Crucial elements in sustaining the changes in the role and contribution of medical laboratories to a high-quality healthcare are the ability of laboratory professionals to: guarantee the quality of laboratory tests irrespective of where they are performed; improve the quality of services; improve clinical outcomes; and perform joint clinical/laboratory research projects. A key factor in effecting the change has been the awareness of the importance of the knowledge and skills required for the new role of laboratory professionals.