The effect of toxins on human health is diverse. In many cases, the relationship between toxins as the causative agent of disease in humans and a host response is difficult to determine. Acute effects of gastroenteritis may be easily identified; however, chronic effects resulting from ingestion of low to moderate levels of toxins can be difficult to recognize. Moreover, the repeated exposure to these sub(acute) doses can lead to their accumulation and (sub)chronic harms. This aspect is of high relevance in the case of lyophilic and stable toxins, such as microbial depsipeptides, cereulide and beauvericin. The risk assessment based approaches, based on in-depth toxicological studies, using in vivo, in vitro and in silico approaches, but also though modification of principles of threshold of toxicological concern (TTC) can be adapted to microbial (bacterial) toxins allowing the definition of levels of no-safety concern. Also the multiexposure, including both multi-toxin and multi-source, and repeated exposure phenomena need to be taken into account and put into perspective with prevalence of low toxin concentrations, total amount of food/toxin ingested, body weight, extended exposure time, and absorption, distribution, metabolism and excretion of the toxins. The aim of this article is to highlight some of the pressing research needs in this domain.