General practitioners (GPs) often find that linear, deductive knowledge does not provide a sufficient map for clinical management. But experience, accompanied by enduring familiarity with individual patients, may offer unique complementary skills to interpret a patient’s symptoms and navigate skilfully through diagnosis, treatment, follow-up and prevention. In this article, we draw attention to the nature of this tacit knowing that is executed by many GPs every day. We argue that the nonlinear, unpredictable complexity of this domain nurtures a particular logic of clinical knowing. This kind of knowledge is not intuition and can to some extent be intersubjectively accessible. We substantiate and discuss how and why general practice research can contribute to knowledge development by transforming reflection-in-action to reflection-on-action. We briefly present some concepts for reflection-on-action of clinical knowing in general practice. The VUCA model (volatility, uncertainty, complexity, ambiguity) embraces dynamic and confusing situations in which agile work (adaptive, flexible and responsive behaviour and cognitive creativity) is assumed to be an appropriate response. Using such perspectives, we may sharpen our gaze and apply reflexivity and analytic elaboration to interpret unique incidents and experiences and appreciate the complexity of general practice. In this way, exploratory research can fertilize general practice and offer innovation to the entire domain of clinical knowledge.