Our understanding of the influence of physicochemical properties of drug candidates on their pharmacokinetic and toxicity profiles has improved substantially in the past 15 years. To investigate the impact of this knowledge, Leeson and St-Gallay analyse the properties of compounds described in patents from 18 leading pharmaceutical companies between 2000 and 2010. Their analysis reveals that a substantial proportion of the industry is still producing compounds with suboptimal physicochemical profiles, indicating that major opportunities remain to reduce compound-related attrition in drug development. The use of predictive biomarkers to identify subsets of patients with cancer who will benefit from specific therapies provides hope of reducing the failure rates of clinical trials, as well as improving therapeutic outcomes. In their Perspective, Beckman and colleagues present a data-driven approach for optimizing the integration of predictive biomarkers into the confirmatory phase of oncology drug development. Tumour cells have evolved various mechanisms to cope with the acidic and hypoxic stress that is associated with their characteristically high rates of metabolism. Interfering with pH regulation in tumours therefore represents a promising novel therapeutic strategy. In their Review, Neri and Supuran discuss the key regulators of pH in cancer cells and consider pH modulators that are currently under development. Breast cancer is commonly treated using classical selective oestrogen receptor (ER) modulators. Gustafsson and colleagues review the current understanding of ER signalling in various diseases, focusing on emerging data suggesting that the development of ER-subtype-selective ligands could provide more effective and safer cancer therapies, with additional potential applications in the treatment of cardiovascular disease, multiple sclerosis and Alzheimer's disease.