Biofouling is defined by the non-specific attachment of biological material (proteins, carbohydrates, prokaryotic cells and higher organisms) to surfaces upon their exposure to any biological fluid. Biofouling is a serious problem in many areas ranging from marine technology, nuclear power plants, dentistry, food processing to biomedical implants. This process can be addressed either actively by chemical compounds inhibiting growth, settlement or biofilm formation, or passively by generating repellent or resistant surfaces. This highlight article gives an overview over different secondary metabolites from cyanobacteria useful in this context. A candidate for active antifouling is nostocarboline, a carboline alkaloid from Nostoc. It has distinct and powerful activities against both prokaryotic and eukaryotic photosynthetic organisms. This compound is a candidate for the replacement of toxic tributyltin (TBT) antifouling coatings. Another passive strategy is presented utilizing the strong binding of anachelin to metal oxide surfaces. This anchor binds polyethyleneglycol (PEG) efficiently to surfaces and renders TiO2 protein resistant. This anchor displays superior properties when compared to dopamine or DOPA, a key constituent in mussel adhesive proteins (MAP). Implications for biomaterials design are discussed.