Depression costs! Each year, billions of dollars are wasted and millions of lives are disrupted because depression is complex, access is limited, treatments are one-size-fits-all, and therapies are trial and error. Nightingale aims to develop innovative solutions using social machines, virtual reality, and pervasive sensor technologies. The goals are: (1) predict an upcoming depression based on personalized features and cognitive modeling, (2) intervene using intelligent synthetic characters and augmented realities with telepresence capabilities for therapists, and (3) provide intelligent tools to users to inform themselves about their condition. Nightingale monitors the user using non-invasive cameras and biosensors, web-based weather data and information about the user’s daily activities. Nightingale intervenes with constructive suggestions, a positive environment, or an alert that medical help is needed. Together, these solutions can better target the right treatments for the right patients at the right time.