A variety of antineoplastic agents is associated with toxicity to healthy tissue and therefore represents a hazard for patients in case of extravasation. The most common risk factors include patient associated and iatrogenic risk factors. Due to the possible complications after extravasation, the knowledge of these risk factors is the basis for prevention, which is of utmost importance. A classification of antineoplastic agents according to the type of tissue damage includes the categories vesicant, irritant, and non-vesicant. Dependent on the extravasated agent, a series of emergency measures should be considered, preferably adhering to a standard operation procedure. There is good evidence for the successful use of antidotes to some antineoplastic agents. These antidotes are dimethylsulfoxide or hyaluronidase, often combined with topical measures such as cooling or application of heat. The application of sodium bicarbonate, sodium thiosulfate, and heparin is not recommended, whereas the usefulness of corticosteroids is still a matter of controversial discussions. Ambiguity in the management of extravasation is often a consequence of limited clinical evidence. Due to our deficient knowledge about some of the administered cytotoxics, there is ongoing need for action even after decades of therapy with antineoplastic agents.