Fungi play an important role in nature and the economy. Being an important source of food, medicine, and enzymes, fungi can also cause human disease, threaten agriculture, and damage buildings. Sequencing of the first fungal genome, Saccharomyces cerevisiae, led to an unprecedented development of the baker's yeast as a model organism and to the building of an entire collection of tools to explore fungal and eukaryotic biology. Large-scale genomic initiatives led to generating a critical mass of data for comparative genomics. New types and large amounts of data posed new challenges for bioinformatics but also opened doors to new applications. This chapter explores the changing landscape of fungal genomics, the challenges in experimental and computational technologies, and the transformations they lead to in biological science.