Health systems all over the world are in a process of transition and may even need a paradigm shift for sustainable development. This is where activism may play a role. This study focused on why some physicians become activists and how these physicians have either achieved successes or failed to do so. This study is inspired by grounded theory. Semi-structured, in-depth interviews were conducted to evaluate the experiences of seven purposefully sampled physician-activists from the Netherlands. Our research suggests that activism originates from an awareness of problems in the area of health inequalities, resulting in moral discomfort combined with a strong drive to speak up against perceived failings, even when personal risks may be involved. Activists that were most successful in achieving political and health changes meandered effectively along the borders of the system, taking care to preserve ties with supporters within that system and, at the same time, taking a relatively isolated position while using strategies to oppose the system. Diverging too much from the system resulted in measures taken by the system to silence them. Successful activism may be regarded as a social and professional skill that may be learned.