Microbiomes can be defined in various ways but, in all cases, they are not simply the sum total of all microbial species that are present—a microbial classification definition does not reflect the complexity of a microbiome. A microbiome includes all biotic and abiotic components—including the environment in which they operate. The influence of natural products on microbiomes was initially primarily as a result of specific antimicrobial properties and hence on perturbation of the system. The link between certain microbial species and disease means that the anti-microbial properties of natural products has been a focus of attention. More recently modulation of microbial properties and behaviour (including aspects such a swarming and biofilm formation) through interaction with quorum sensing molecules has become a target. This has increased as the importance of pathogen:host interactions have been the subject of scrutiny and study. While some fungally-derived microbial natural products (e.g. penicillins) are potent antimicrobial (and, in particular, antibacterial) agents, others that are grouped under the heading of mycotoxins are toxic to mammals and prevention of their ingestion has attracted significant attention. Microbiomes exist within a world of complex interactions that include all biotic and abiotic components and their reactions.