Despite the interconnected redundancies and safeguards of the immune system, some microbes manage to overcome these barriers. In some cases, the pathogen evolves to become less harmful and coexists with the host; indeed, pathogens in nature are far outnumbered by closely related strains that are harmless or even beneficial to their hosts. In other cases, however, evolution generates a never-ending arms race between pathogen and host. In some cases the pathogens currently have the upper hand and kill humans one million times their size. What makes a pathogen different from a commensal organism? What strategies contribute to the success of a pathogen? The answer varies, depending on the pathogen. Some bacterial pathogens can avoid being phagocytosed by host cells, whereas others actively encourage it. Curiously, some bacterial pathogens develop a latent, undetectable stage in the host, and emerge later to cause disease. Some pathogens efficiently slay their hosts. Others persist for many years without killing. Which is the more successful pathogenic strategy? This chapter explores the strategies different bacterial and viral pathogens use to grow within human hosts.