Hepatotoxic microcystins that are produced by freshwater cyanobacteria pose a risk to public health. These compounds may be eliminated by enzymatic degradation. Here, we review the enzymatic pathways for the degradation of these hepatotoxins, some of which are newly discovered processes. The efficiencies of microcystin biodegradation pathways are documented in several papers and are compared here. Additionally, a comprehensive description of the microcystin enzymatic degradation scheme has been supplemented with a proposal for a new biodegradation pathway. Critical comments on less documented hypotheses are also included. The genetic aspects of biodegradation activity are discussed in detail. We also describe some methods that are useful for studying the biological decomposition of microcystins, including screening for microcystin degraders and detecting microcystin degradation products, with an emphasis on mass spectrometric methodology.