Phenomenon: Pharmacology is a fundamental healthcare discipline, but it can be difficult and counterintuitive for learners to learn. Navigation toward understanding pharmacology can be troublesome, but once the threshold to comprehension is crossed, learners can experience a transformative shift in their ways of thinking and practicing. We conducted an in-depth examination of threshold concepts within pharmacology, aiming to identify and prioritize their learning to improve the medical curriculum and enhance medical treatment and patient safety. Approach: We carried out a consensus generation process using the Nominal Group Technique (NGT) to identify potential threshold concepts in pharmacology. Participant groups of pharmacology experts and medical students considered, identified, reviewed, and ranked potential pharmacology threshold concepts within their own group. Then, using a logical, step-by-step approach, we combined the final ranked data from these multiple NGT sessions. We further analyzed these data using an abductive analysis approach; data were coded, categorized, reorganized, and conceptually mapped after critical evaluation. Conceptual themes were established corresponding to different phases of cognitive schema development. Findings: Six comprehensive conceptual themes were identified: Drug Mechanism of Action; Pharmacotherapeutics; Pharmacokinetics; Drug Receptor Interactions; Drug Terminology and Nomenclature; and Signaling Pathways. These concepts align with many of the key attributes of threshold concepts (e.g., troublesome, integrative and transformative). The cognitive schematic themes generated were (i) acquisition-troublesome; (ii) acquisition-transformative; (iii) automation-troublesome; (iv) automation-transformative. Insights: Transformative learning involves different stages of cognitive schema evolution, including acquisition, elaboration, and automation, and is influenced by both the inherent challenges of the concepts and limitations of human cognition. The high interactivity of these troublesome concepts challenge schema acquisition and automation. Troublesome concepts underpinning procedures or skills, while not easily explained by cognitive rules, can lead to slow, awkward, error-prone performance, creating additional barriers for practice. Integrating concepts into a coherent structure leads to the irreversible assimilation of knowledge and the transferability of both knowledge and skills, influencing learners’ epistemological transitions and ontological transformations at theoretical and professional levels. Further work on designing instructional models around assisting and automating schemas around identified troublesome knowledge, while addressing the impact of cognitive load, has the potential to promote transformational learning.