The results of MCSS therapy for patients with severe heart failure are improving, and there are increasing numbers of implants as device therapy enters the era of permanent use (i.e., destination therapy). Device-related infection of implanted pumps and sepsis remain important risk factors for death, and once infections are established on biomaterial surfaces they usually persist despite prolonged antimicrobial therapy. This paper covers the topic of infection in mechanical circulatory support. Methods to prevent and manage infection are described. Recent information from the field of microbiology that is relevant to understanding device-related infection is reviewed, including the mechanisms for microbial adhesion to prosthetic surfaces, quorum sensing, and biofilm formation. Characteristics that are important to antimicrobial resistance of microbes dwelling in biofilms are described (e.g. responses to microenvironmental conditions that result in resistance to antibiotics). This information may lead to new therapies that further diminish rates of device infection, and allow complete eradication of infections when they occur. © Wichtig Editore, 2007.