Filamentous fungi produce a wide variety of bioactive secondary metabolites that play roles in development and fitness. In the pre-genomic era of Botrytis cinerea research, already about eight families of secondary metabolites have been isolated from in vitro mycelium. In particular, the predominant metabolites botrydial and botcinic acid were identified as two unspecific phytotoxins contributing to the necrotrophic and polyphagous lifestyle of the fungus. Sequencing and annotation of the complete genome revealed more than 40 clusters of genes dedicated to the synthesis of polyketides, terpenes, non-ribosomal peptides and alkaloids which indicates that B. cinerea has the potential to produce many metabolites that have not been described so far. By a combination of transcriptomic, mutagenesis and metabolomic approaches the genes responsible for the production of botcinic acid and botrydial were identified and significant progress was made in the elucidation of the corresponding polyketidic and terpenic biosynthesis pathways. Mutagenesis also revealed that, although these two toxins play together a significant role in plant tissues colonization, some of the other secondary metabolites seem to be crucial for the necrotrophic processes as well. A major bottleneck in the identification of these compounds is that they are not produced in sufficient amounts during standard in vitro conditions. However, progress in understanding the regulation of fungal secondary metabolism, through transcription factors and epigenetic mechanisms, provide new strategies to “wake up” biosynthetic genes during in vitro growth. This will pave the way for the characterization of these metabolites that play an important if not essential role in B. cinerea virulence.