Big Data, often defined according to the 5V model (volume, velocity, variety, veracity and value), is seen as the key towards personalized healthcare. However, it also confronts us with new technological and ethical challenges that require more sophisticated data management tools and data analysis techniques. This vision paper aims to better understand the technological and ethical challenges we face when using and managing Big Data in healthcare as well as the way in which it impacts our way of working, our health, and our wellbeing. A mixed-methods approach (including a focus group, interviews, and an analysis of social media) was used to gain a broader picture about the pros and cons of using Big Data for personalized healthcare from three different perspectives: Big Data experts, healthcare workers, and the online public. All groups acknowledge the positive aspects of applying Big Data in healthcare, touching upon a wide array of issues, both scientifically and socially. By sharing health data, value can be created that goes beyond the individual patient. The Big Data revolution in healthcare is seen as a promising and innovative development. Yet potential facilitators and barriers need to be faced first to reach its full potential. Concerns were raised about privacy, trust, reliability, safety, purpose limitation, liability, profiling, data ownership, and loss of autonomy. Also, the importance of adding the people-centered view to the rather data-centered 5V model is stressed, in order to get a grip on the opportunities for using Big Data in personalized healthcare. People should be aware that the development of Big Data advancements is not self-evident.