Persistent colonization of a host by a microbe is rarely an accident. Rather than the death of the host or the elimination of the invader, persistence requires coexistence, which must be governed by equilibrium relationships that are stable during the majority of the interaction. Traditionally such relationships are divided into three exclusive categories: parasitism, commensalism, and symbiosis (1). Parasitism is a relationship in which one species benefits at the expense of the other. Most of the pathogenic organisms that medical microbiologists study fall into this category. The expense of microbial parasitism is often the consequence of the microbe’s requirement for transmission to a new host. The pulmonary cavities caused by Mycobacterium tuberculosis are one example of this phenomenon. Commensalism may be defined as a relationship in which one species derives benefit and the other is unharmed. We consider the “normal microbial flora” of humans to mostly consist of such opportunistic organisms. Symbiosis is the biological association of two or more species to their mutual benefit. Our best-understood endosymbionts are mitochondria (2), but symbiosis in humans otherwise has not been well-explored (3). Examples of these relationships in human biology are illustrated in Table I. However, these classifications do not seem sufficient. Even organisms that are classified as commensals or symbionts might ultimately cause disease, such as endocarditis caused by oral streptococci, or intraabdominal abscesses caused by Bacteroides species. The term “amphibiotic” has been used to designate organisms that may be either beneficial or disease-causing, depending on context (4). In any event, since all of these concepts are biological, they must be considered in terms of evolutionary constraints. For such analysis, efficiency of transmission, effects on reproductive ability of the host, and effects on total populations rather than on isolated individuals also must be considered. For example, an amphibiotic microbe could be a symbiont during a host’s reproductive period, but a parasite thereafter. As such, it is instructive to study the gram-negative bacteria, Helicobacter pylori, that persistently colonize the stomachs of humans and other primates. Understanding their intercourse with humans is important because of their medical significance (5), but also because such analyses provide paradigms of host–microbial interactions that may have applicability to other clinically significant organisms. Microbiologists in the 19th century considered these organisms as commensals, but since their rediscovery by Marshall and Warren, most current investigators believe that they are strictly parasites (6). The thesis proposed herein is that the relationships that H. pylori have with humans may encompass each of the three prototypes illustrated in Table I. I maintain that these relationships are fluid and depend on the population biology of both the host and the microbes, each of which are affected by environmental constraints. Microbes that are symbionts in one era may become parasites when circumstances change, and importantly, vice versa.