Mycobacterium chimaera (MC), a member of the Mycobacterium avium complex, can cause infections in patients after open-heart surgery due to contaminated heater–cooler units (HCUs). The transmission route of HCU-related MC infection is non-inhalational, and infection can occur in patients without previously known immune deficiency. Patients may develop endocarditis of the prosthetic valve, infection of the vascular graft, and/or manifestations of disseminated mycobacterial infection (splenomegaly, arthritis, hepatitis, nephritis, myocarditis, etc.). MC infections have serious outcomes (30–50% recurrence rate, 20–67% mortality rate). In 2015, an international outbreak of M. chimaera infections among patients undergoing cardiothoracic surgeries was associated with exposure to contaminated LivaNova 3T HCUs (formerly Stöckert 3T heater–cooler system, London, United Kingdom). In response to the global outbreak, many international agencies have issued directives and recommendations in order to reduce the risk of MC infection in cardiac surgery. Whole-genome sequencing (WGS) technology can be used to describe the global spread and dynamics of MC infections, to characterize local outbreaks, and also to identify sources of infection in hospital settings. In order to minimize the risk of contamination of HCUs and reduce the risk of patient infection, it is imperative that healthcare facilities establish a program of regular cleaning and disinfection maintenance procedures as well as monitoring of the water used and the air in the operating room, in accordance with the manufacturer’s procedure.