The enormous biodiversity developed by Nature during several billion years of evolution has offered a wealth of chemically diverse compounds that have been preselected to modulate biochemical pathways, thus representing a rich source of lead molecules in drug discovery. As metabolites represent the final downstream products of gene transcription, changes in the metabolome are amplified relative to changes in transcriptome and proteome systems. Hence, their analysis can provide different but complementary information about biological function as compared to transcription or expression profiles. The modern development of new analytical methodologies allows the natural product chemists to cope with several troubles presented by the natural molecular high chemo-diversity from different viewpoints and with better perspectives than before. In this seminar I will present few cases taken from our recent research, outlining the main aspects (structure elucidation, total synthesis, ab initio computations) which currently represent the main bottlenecks in natural products chemistry. Last results from our recent adventures in the lipids world will be finally discussed.