Susceptibility of individuals and groups to toxicants depends on complex interactions involving the host, environment, and other exposures. Apiary diagnostic investigation and honey bee health are truly population medicine: the colony is the patient. Here we provide basic information on the application of toxicology to the testing of domestic honey bees, and, in light of recent research, expand on some of the challenges of interpreting analytical chemistry findings as they pertain to hive health. The hive is an efficiently organized system of wax cells used to store brood, honey, and bee bread, and is protected by the bee-procured antimicrobial compound propolis. Toxicants can affect individual workers outside or inside the hive, with disease processes that range from acute to chronic and subclinical to lethal. Toxicants can impact brood and contaminate honey, bee bread, and structural wax. We provide an overview of important natural and synthetic toxicants to which honey bees are exposed; behavioral, husbandry, and external environmental factors influencing exposure; short- and long-term impacts of toxicant exposure on individual bee and colony health; and the convergent impacts of stress, nutrition, infectious disease, and toxicant exposures on colony health. Current and potential future toxicology testing options are included. Common contaminants in apiary products consumed or used by humans (honey, wax, pollen), their sources, and the potential need for product testing are also noted.