Cyanobacteria have colonized almost all terrestrial and aquatic ecosystems although they are more abundant in freshwaters, where they can grow up to very high densities, forming blooms and scums. Increasing occurrence of blooms, in terms of extension and frequency, associated with excess of nutrients due to anthropogenic activities and climate changes, has given rise to some concern for human health and animal life exposed to some secondary metabolites which are toxic (cyanotoxins). Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of human poisonings have been recorded after acute/short-term exposure; the most serious known episode occurred in Brazil, where 56 out of 130 hemodialyzed patients died after treatment with water accidentally contaminated with cyanotoxins. However, the repeated/chronic exposure to low cyanotoxin levels are a more critical issue. In those areas where people are more dependent from stored (in some cases desalinated) drinking water in reservoir, such as arid and developing countries, this problem seems to be of higher concern. Humans may be orally exposed to cyanotoxins by drinking contaminated water, consuming cyanotoxin-containing freshwater fish, crops, vegetables and food supplements, or ingesting water during recreational activities. During recreational, sport and professional activities (i.e., fishing) in contaminated waters dermal and inhalation exposure may also occur. The known cyanotoxins have a large spectrum of toxic effects from acute gastroenteritis and flulike symptoms, to hepato- and nephro-toxicity, neurotoxic effects and tumor promotion, depending on the toxin involved and the exposure scenarios. Despite the relevance of these effects, data on the kinetic behavior, toxicological profile and exposure levels are still scant and often limited to few variants. Nevertheless, it is possible to use the available data to derive some reference values as WHO did, although with a high degree of uncertainty.