Phagocytosis is an ancient cellular function. However, professional phagocytes have evolved only in higher organisms, where they play an important role in host defence. Professional phagocytes are capable of engulfing relatively large microorganisms and killing them with a combination of various microbicidal systems. Crucial killing mechanisms of phagocytes include superoxide generation by phagocyte NADPH oxidase and release of microbicidal proteins through exocytosis of performed granules. Phagocytes are also able to interfere with microbial growth through alteration of the phagosomal ionic environment (acidification, iron depletion). While the microbicidal mechanisms of phagocytes are extremely efficient and capable of killing most microorganisms, pathogenic microorganisms have developed mechanisms to resist phagocytes. Microorganisms capable of surviving within phagocytes are rare, but represent very successful pathogens, such as Mycobacterium tuberculosis. Other pathogens, such as S. aureus, have developed strategies to evade phagocytosis. How microorganisms are phagocytosed and killed, and why certain pathogens resist these mechanisms, are crucial questions for an understanding of the pathogenesis of infectious diseases and the development of innovative treatment approaches.