The dark side of opioids' ability to deaden pain is the risk that they might kill their user. The same brain receptors that blunt pain when drugs such as morphine or oxycodone bind to them can also signal breathing to slow down. It's this respiratory suppression that causes most overdose deaths. So scientists have hoped to design opioids that are "biased" toward activating painkilling signals while leaving respiratory signaling alone. Several companies have cropped up to develop and test biased opioids. But two new studies in mice contest a key hypothesis underlying these efforts—that a signaling protein called beta-arrestin2 is fundamental to opioids' effect on breathing.