As well as the unremitting scientific challenges peppering the process of R&D, moral considerations also abound. Competing for limited resources naturally leads to conflicts, and the ethical issues surrounding some of these conflicts are considered in April's edition of Nature Reviews Drug Discovery. Can academic institutions retain their independence when they receive money from, or enter into collaborations with, industry? In her Perspective article, Margaret Somerville discusses the problems that can arise from such arrangements, and also considers to whom the values of academic freedom are most important. Ethical and social concerns are also the theme of Amalia Issa's Review article on pharmacogenomic profiling. Determining genotype–phenotype correlations for drug responsiveness and adverse events is an exciting goal, but must be considered in the light of the associated social risks and economic issues. Focusing on a different social problem, Stephen O'Rahilly and colleagues review obesity therapy and help us to appreciate the special nature of this disease. Complementing this Review, this month's From the Analyst's Couch analyses the expanding market for obesity drugs. Two other Reviews deal with groups of diseases that urgently require new therapeutic approaches — cancers and protein-folding diseases. James Sacchettini and Jeffery Kelly review therapeutic strategies for human amyloid diseases, and Ricky Johnstone weighs the evidence for histone-deacetylase inhibitors as novel drugs for the treatment of cancer. In the lead Review, Timothy Willson and Steven Kliewer examine the roles of the nuclear receptors PXR and CAR as xenobiotic sensors, and discuss the application of this knowledge to toxicological screening. Philip Cohen completes the Perspective section with a Timeline that summarizes the major advances that have shaped the burgeoning field of protein-kinase inhibitors.