The metabolome of an organism consists in the totality of the small molecules present in this organism at a given time. Unlike genome, transcriptome or proteome, it represents the real-time content of the living organism at the metabolic level. In order to understand complex biological interactions between cells, tissues, organs or individuals in a specific ecosystem, it is fundamental to first identify all the components, i.e. all the molecules that can be encountered. Over the last decade, identification of small biologically generated compounds, the metabolites, has emerged as the main issue in the field of metabolomics and despite all the great efforts of the community during the last years only a relatively small number of compounds have been referenced in accessible databases, often with only hypothetical structures. Herein we propose to discuss the philosophical aspects of the important question ”what is a known natural product?” in order to move forward to a new paradigm in metabolite identification: identifying the real from the possible.

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