[Figure not available: see fulltext.] The aim of this review is to present the entire range of cyclooctynes that are currently known in the literature. We provide a generalized and systematic overview of methods for their synthesis and consider the applications of cyclooctynes for the purposes of molecular biology and cellular engineering. The importance of cyclooctynes for [3+2] azide-alkyne cycloaddition is demonstrated, as the high reactivity of cyclooctynes allows to perform this reaction under mild conditions without a catalyst.