The decline in productivity of the pharmaceutical industry may stem, at least in part, from underestimating the complexity of human disease. While a disease-relevant gene or protein may initially seem to be an attractive drug target, appreciating its role in the network of pathways involved in a disease provides a better perspective for making this decision. In some cases, off-target effects or redundancy in the network can negate the potential efficacy of a new drug. Even a successful drug, such as imatinib (Gleevec), may be less selective than originally thought, resulting in important, and sometimes useful, consequences. Advances in the area of network biology provide an important perspective on the potential of a drug target, and are being applied to various diseases. The impact of these advances on the field of drug discovery is assessed.