Could creating a research environment analogous to that of a small biotechnology company help to revitalize innovation in large pharmaceutical companies? This question, which has been an important consideration in the restructuring of research and development (R&D) at several companies, is among those investigated in a Perspective article on entrepreneurship in the pharmaceutical industry this month from Douglas and colleagues, based on interviews with 26 leaders of R&D at pharmaceutical and biotechnology companies. Our second Perspective this month, by Drag and Salvesen, discusses how new insights into protease biology and structure are shaping emerging approaches to identifying therapeutic inhibitors, such as targeting allosteric sites, which could help in developing novel drugs for treating cancer and inflammatory diseases, among others. Approaches to targeting chronic inflammatory diseases, such as rheumatoid arthritis, are also considered in a Review by Kopf and colleagues, who highlight the potential of recent insights into cytokine networks and technical progress in blocking cytokines in vivo to lead to improved therapeutics. An emerging strategy for treating inflammatory disorders — harnessing the properties of carbon monoxide (CO) gas and CO-releasing molecules — is among the applications of the molecules highlighted by Motterlini and Otterbein, who outline the role of CO as an endogenous cytoprotective and homeostatic molecule and review its beneficial effects in preclinical models of a range of diseases. Finally, Ostrosky-Zeichner and colleagues give an overview of the most promising small molecules in the antifungal pipeline and discuss how improved diagnostics and new developments in vaccines and antibody-based immunotherapy are offering alternative strategies for tackling invasive fungal infections.