The development of sepsis drugs—like the patients these agents aim to treat—is in desperate need of resuscitation. Last autumn, Eli Lilly pulled the only approved antisepsis drug from global markets, and in May the world found out exactly why: the drug, a recombinant from of activated protein C known as Xigris, proved no better than placebo at preventing death in a global post-marketing trial of 1,700 people at high-risk of septic shock (N. Engl. J. Med. 366, 2055–2064, 2012). Worryingly, critical-care specialists now have no drug therapies they can turn to specifically for the treatment of severe sepsis, a condition that afflicts around 18 million people worldwide each year.

The news isn't all bad, though. Mortality rates from sepsis have been dropping in recent years, thanks to improvements in hospital care and a heightened awareness of the deadly disease. And the drug pipeline is filling once again with new treatment options targeting every stage of the disease process. Nonetheless, severe sepsis still kills around one in four people it affects, and proving that experimental therapies are helpful for treating such a variable disease—one that might best be described as a nonspecific syndrome—remains a major hurdle. In the pages that follow, we highlight how sepsis researchers are working to overcome those challenges, taking aim at every step in drug development and medical practice.