Background In routine practice, general practitioners (GPs) see many patients for whom treatment might not be necessary, or evidence-based treatments are not available, yet often a treatment is prescribed. We denote such situations as therapeutically indeterminate. We aimed to investigate 1) whether therapeutically indeterminate situations play a role in the accounts of GPs in their practical work; 2) the role of complementary and alternative medicine (CAM) modalities or non-specific therapies, and of other strategies used in handling therapeutically indeterminate situations; and 3) factors associated with preferences for specific strategies. Methods We performed semi-structured, individual face-to-face interviews with 20 purposively sampled, experienced GPs from Bavaria, Germany. A grounded theory approach was used for data analysis. Results Participants reported that therapeutically indeterminate situations recur often in their daily practice. Professionally legitimate strategies such as empathetic consultations without providing a treatment intervention did not seem to suffice for coping with all of these situations. CAM treatments were used frequently, but motives varied. While some participants were convinced that these treatments were active and effective, others were uncertain or had doubts and used them as a relational tool, as a non-specific treatment or as a beneficial placebo. Conventional drugs were also used in a non-specific manner or despite doubts regarding the risk-benefit ratio. The extent to which GPs felt responsible for offering solutions in therapeutically indeterminate situations seemed to influence their preference for specific strategies. Conclusion Our results demonstrate the important role of CAM and the somewhat smaller role of non-specific therapies for German general practitioners in dealing with therapeutically indeterminate situations. The concept of therapeutically indeterminate situations may be helpful in better understanding why many general practitioners treat patients in situations where treatment does not appear to be clearly indicated.