Models that summarize rich information about biological systems can be a good way to understand how to manipulate those systems. I 19ll talk about how we have leveraged genomic studies of sleep to model gene networks identify potential drug targets for sleep and related neurological and psychiatric conditions. Brain-penetrant compounds offer a fine opportunity to test these models and also hold out the possibility of eventually identifying new indications for marketed and investigational therapeutics. Finally, using examples from infectious disease and cancer, I 19ll discuss how precise sequencing technologies allow us to monitor and model the development of resistance to drugs, potentially improving therapy at the same time we validate drug targets and answer fundamental questions about the biology of disease.