A series of genome projects have uncovered an astonishing molecular diversity of cytochrome P450s in the fungal kingdom. Fungal P450s discovered from such projects are often categorized into novel families and subfamilies. It thus appears that the divergence of fungal P450s is greater than of animal, plant, or bacterial P450s. The tremendous variation implies that fungi have vigorously diversified P450 functions to meet novel metabolic needs. To better understand the metabolic diversity of fungi, one must undertake the challenging task of exploiting the catalytic functions of numerous P450s. A compilation of P450 functions will also enable us to utilize their catalytic potentials in biotechnology. Experimental screening remains essential however, to elucidate the catalytic potentials of individual P450s. This review outlines the molecular and genomic aspects of fungal P450s, and introduces new functions revealed by functionomic studies using a recently developed, rapid, functional screening system.