The introduction of highly active antiretroviral therapy in the 1990s revolutionized the treatment of patients infected with human immunodeficiency virus (HIV). However, there is a continuing need for novel anti-HIV therapies to combat viral resistance. In our sixth 'Case history', Dani Bolognesi and colleagues from Trimeris and Roche describe the discovery and development of enfuvirtide, the first approved inhibitor of HIV fusion. This month's 'Fresh from the Pipeline' also focuses on a drug that has been approved for treating patients whose disease is not adequately controlled by current therapies: omalizumab, a biologic that targets a key mediator of the allergic response, which was recently approved by the US FDA for the treatment of allergic asthma. A growing number of biologics are facing patent expiry, but, as discussed in 'From the Analyst's Couch', the development of biogenerics is considerably more complicated than the development of generic small-molecule drugs. All new drugs must undergo a battery of preclinical tests that comply with detailed regulatory guidelines. Peter Greaves and co-authors review the principles and the available evidence that supports the design and conduct of preclinical studies to permit safe and effective first-dose-to-human studies. Drugs that target neuronal excitotoxicity are presently used to treat Parkinson's and Alzheimer's diseases. Ashley Bush and colleagues suggest that targeting an upstream cause of excitotoxicity – oxidative stress – might lead to the development of new treatments for such neurodegenerative disorders. Ion channel dysfunction is also implicated in neurodegeneration. Rounding off this issue, we present the opinions of twenty experts on various aspects of ion channel research in the first of our 'Twenty Questions' sections.