Huey Lewis and the News summed it up nicely in their 1980s hit record: 'I want a new drug, one that won't make me sick, one that won't make me crash my car, or make me feel three feet thick'. The song could be an anthem for drug discovery in the pharmaceutical industry. We all want new and better drugs with fewer side effects, which are effective for combating the major diseases of our time: cancer, heart disease, obesity and autoimmune diseases. How do we get these new drugs? There are currently some new ideas in drug discovery, centered on that staple diet of the pharmaceutical industry, the G-protein-coupled receptor (GPCR) superfamily. In silico methods, employing receptor-based modeling, offer a more rational approach in the design of drugs targeting GPCRs. These approaches can be used to understand receptor selectivity and species specificity of drugs that interact with GPCRs. In addition, there are various novel approaches, such as the design and potential utility of drugs that target more than one GPCR ('dual specificity' drugs).