Cytochromes P450 (CYP) have been expressed in a variety of systems such as mammalian cells, yeast, and bacteria. The bacterial system is technically the least demanding and provides large amounts of catalytically active P450s for metabolic and structural studies relating to preclinical drug development. This chapter provides a detailed technical description of the processes that allow the coexpression of various CYP isoforms together with CYP reductase in Escherichia coli and gives some examples of the results that can be achieved for the expression of human P450s.