Sclerotinia sclerotiorum is one of the worst soilborne pathogens around the world. Despite its economic importance, it has been understudied due to its multinucleate cells, making molecular genetic analyses difficult. We recently developed a forward genetics pipeline in S. sclerotiorum, which combines mutant screening with high-throughput next-generation sequencing to enable quick gene discovery. From analyses of mutants that cannot form sclerotia and/or cannot cause diseases, we uncovered the importance of RAS signaling, cAMP, autophagy, and MAPK kinase cascades to the basic biology of Sclerotinia sclerotiorum, including sclerotia formation and virulence. We also serendipitously found that chromosomes in haploid cells of Sclerotinia sclerotiorum and Botrytis cinerea are separated into different nuclei, with each nucleus containing a fraction of the chromosomes. The partition of chromosome subsets into distinct nuclei brings new questions and opens fresh avenues for chromosome biology.