Many past studies have focused on uncertainty in medical practice, yet it is still not well understood in the field of family medicine, especially among residents. The aim of this study was to examine situations in which residents experience uncertainty and the coping strategies they use to deal with it. The results may have implications for advanced training programs and the specialist training in family medicine. We conducted semistandardized interviews with 15 residents and young family doctors from Hesse, Germany and asked them to describe cases in which they experienced uncertainty. In total, 40 cases were reported. Using established methods, we derived a coding system with different categories. Uncertainty occurred in a broad and heterogenous range of cases, and it often involved complex interaction of biomedical, interpersonal, and psychosocial factors. The participants described various strategies that were helpful in dealing with the three different types of uncertainty. To deal with biomedical uncertainty, the residents primarily found information-seeking and consulting more experienced colleagues to be useful. In dealing with interpersonal and psychosocial uncertainty, they applied reflective strategies. Participants suggested open communication and honest dialogue about uncertainty and the thematization of the topic at much earlier stages (eg, during medical studies). Family medicine residents experience uncertainty as an important part of their daily work. They do not necessarily interpret it as a negative phenomenon. Instead, uncertain situations often accompany learning effectiveness and an increase of self-confidence.