Extant anuran amphibians originate from an evolutionary intersection eventually leading to fully terrestrial tetrapods. In many ways, they have to deal with exposure to both terrestrial and aquatic environments: (i) phylogenetically, as derivatives of the first tetrapod group that conquered the terrestrial environment in evolution; (ii) ontogenetically, with a development that includes aquatic and terrestrial stages connected via metamorphic remodeling; and (iii) individually, with common changes in habitat during the life cycle. Our knowledge about the structural organization and function of the amphibian olfactory system and its relevance still lags behind findings on mammals. It is a formidable challenge to reveal underlying general principles of circuity-related, cellular, and molecular properties that are beneficial for an optimized sense of smell in water and air. Recent findings in structural organization coupled with behavioral observations could help to understand the importance of the sense of smell in this evolutionarily important animal group. We describe the structure of the peripheral olfactory organ, the olfactory bulb, and higher olfactory centers on a tissue, cellular, and molecular levels. Differences and similarities between the olfactory systems of anurans and other vertebrates are reviewed. Special emphasis lies on adaptations that are connected to the distinct demands of olfaction in water and air environment. These particular adaptations are discussed in light of evolutionary trends, ontogenetic development, and ecological demands.