Heterocyclic compounds by far outnumber the homocyclic PAHs. In addition, they are often more soluble in water, which may imply a greater biological significance of these heterocycles. Yet, most research focuses on the homocyclics, based on the implicit assumption that the mostly higher concentration of the homocyclics rank these compounds as priority compounds. This review critically examines the available evidence and poses questions on the biological activity and environmental risk of one small group of heterocyclics, the azaarenes, which contain one nitrogen atom in one of the aromatic rings. In different sections, the biotransformation and different types of toxicity are discussed in comparison to those of homocyclic PAHs. The last section focuses on the implications for risk assessment of PAHs. Two- and three-ringed azaarenes can be relatively easily transformed by bacteria, fungi, invertebrates, and vertebrates. The presence of the N-moiety in the smaller azaarenes leads to metabolic routes that partly differ from those of the homoaromatic analogues. Major metabolic products of the azaarenes appear to be ketones and mono- or dihydroxylated azaarenes. Microorganisms can further degrade these into multiple oxygen-containing compounds or they can open up the aza-containing aromatic ring and fully metabolize the products. Fungi and vertebrates were shown to produce the mutagenic dihydrodiol metabolites. The metabolism of the larger azaarenes in vertebrates proceeds analogous to homoaromatic PAH, because in these larger molecules the N-moiety has less influence. Transformation of the larger azaarenes by microorganisms proceeds much slower if occurring at all. Direct toxicity data of azaarenes are mostly restricted to the effects of acridine and quinoline on a relatively small number of species. From this limited set it becomes clear that differences between species are relatively small. As with homocyclic PAHs, toxicity generally increases with increasing number of rings, and baseline toxicity models based on homocyclic PAHs do apply. Toxicity differences between isomers indicate that azaarene toxicity cannot be explained by molecular size-related parameters alone, indicating that electronic forces may be important as well. Considering chronic toxicity it becomes clear that the often-used acute-to-chronic-ratios often underestimate specific chronic toxicity, even within the very limited set of chronic data available. In contrast with homocyclic PAHs, photodegradation of azaarenes shows the same degradation products as biological transformation involving monooxygenases. In general, as for homocyclic PAHs, the degree of phototoxicity is related to the UV absorption characteristics of the azaarenes, which makes it possible to apply the QSAR models developed for homocyclic PAHs to azaarenes as well. Recent research on algae showed that UV-A is the main cause of photoenhanced toxicity. Together with the fact that in the water column UV-B is almost absent, this clearly demonstrates the relevance of phototoxicity in the field. Mutagenicity of azaarenes generally proceeds through similar pathways as in homocyclic PAHs, with bay region diol epoxides as major genotoxic metabolites. The N-moiety can, however, result in differences in genotoxic activities between isomers. Carcinogenicity of azaarenes in mammals is generally restricted to four-ringed and larger structures, and mechanisms leading to cancer are similar to those of homocyclic aromatics. An exception to this general pattern is quinoline, which has been shown to induce liver cancer. The present risk assessment for PAHs is solely based on homocyclic PAHs. Yet, from the present review it becomes clear that this approach fails to protect against a vast number of heterocyclic compounds and biotransformation products that may exhibit stronger or other toxic effects than their homocyclic analogues. Therefore, incorporating the role of heterocyclic compounds and their metabolism appears to be a necessity for a reliable risk assessment for polycyclic aromatic compounds. In addition, reliable long-term protection against PAHs demands data on chronic toxicity, including teratogenicity, both for homocyclic as for heterocyclic compounds.