The Well-being of Adolescents in Vulnerable Environments (WAVE) is a global study of young people living in disadvantaged urban communities from Baltimore, MD, Johannesburg, South Africa, Shanghai, China, New Delhi, India and Ibadan, Nigeria. WAVE was launched in the summer of 2011 to: 1) explore adolescents' perceived health and their top health challenges; and 2) describe the factors that adolescents perceive to be related to their health and health care utilization. Researchers in each site conducted in-depth interviews among adolescents; community mapping and focus groups among adolescents; a Photovoice methodology, in which adolescents were trained in photography and took photos of the meaning of 'health' in their communities; and key informant interviews among adults who work with young people. A total 529 participants from across the sites were included in the analysis. Findings from the study showed that gender played a large role with regards to what adolescents considered as their top health challenges. Among females, sexual and reproductive health problems were primary health challenges, whereas among males, tobacco, drug, and alcohol consumption was of highest concern, which often resulted into acts of violence. Personal safety was also a top concern among males and females from Baltimore and Johannesburg, and among females in New Delhi and Ibadan. Factors perceived to influence health the most were the physical environment, which was characterized by inadequate sanitation and over-crowded buildings, and the social environment, which varied in influence by gender and site. Regardless of the study site, adolescents did not consider physical health as a top priority and very few felt the need to seek health care services. This study highlights the need to focus on underlying structural and social factors for promoting health and well-being among adolescents in disadvantaged urban environments.