Medical physiology is known to be a complex area where students develop significant errors in conceptual understanding. Students’ knowledge is often bound to situational descriptions rather than underlying principles. This study explores how medical students discern and process underlying principles in physiology. Indepth interviews, where students elaborated on principles related to blood pressure and blood pressure regulation, were carried out with 16 medical students in a problem-based learning curriculum. A qualitative, phenomenographic approach was used, and interviews were audiotaped, transcribed, qualitatively analyzed, and categorized. Four categories were outlined. The underlying principles were conceived as follows: 1) general conditions for body function at a specified time point, 2) transferable phenomena between organ systems and time points, 3) conditionally transferable phenomena between organ systems and time points, and 4) cognitive constructions of limited value in medical physiology. The results offers insights into students’ thinking about underlying principles in physiology and suggest how understanding can be challenged to stimulate deep-level processing of underlying principles rather than situational descriptions of physiology. A complex conception of underlying principles includes an ability to problemize phenomena beyond long causal reasoning chains, which is often rewarded in traditional examinations and tests. Keywords for problemized processing are as follows: comparisons, differences, similarities, conditions, context, relevance, multiple sampling, connections, and dependencies.