Efforts to develop new therapies for diseases that represent a massive burden in the developing world, such as malaria, have gained new impetus in recent years, stimulated in part by philanthropic funding. Two reviews this month describe approaches to addressing some of the major challenges such efforts are presently facing. Deen and Clemens consider issues in the design and implementation of vaccine trials in less-developed countries, whereas Nwaka and Hudson discuss strategies to alleviate a key bottleneck in the pipeline for novel drugs for tropical diseases — lead discovery. Another significant bottleneck in drug development in general is biomarker qualification, and in an article in our series on biomarkers Williams and colleagues propose a cost-effectiveness approach to tackle this problem. Also part of an ongoing series — in this case, on model organisms — is a review by Van Dam and De Deyn that summarizes and evaluates rodent models of dementia, which will have a key role in assessing novel therapeutics for disorders such as Alzheimer's disease. Like Alzheimer's, obesity is the focus of major efforts to develop new drugs at present, and in their review Cooke and Bloom overview the pipeline for obesity therapies, with an emphasis on gut peptides. And opening our review section, Rommel and colleagues highlight efforts to capitalize on the promising potential of the signalling molecule phosphatidylinositol 3-kinase-γ as a target for the treatment of inflammatory disease. Finally, this month we are pleased to present the first article in a new careers section profiling people involved with the biopharma industry — Career snapshots — which will aim to provide insights on a wide range of roles, as well as career development tips.