PURPOSE OF REVIEW: This review presents some difficulties encountered to develop and translate immunonutrition into clinical practice, and suggests moving forward to a pharmaconutrition approach. RECENT FINDINGS: Immunonutrition suffers from inconclusive and contradictory data due to the design of many of experiments and clinical studies conducted so far. The concept of a single immunonutrient formula applicable to various types of patients has also contributed to leave the medical world in a state of uncertainty. We propose to move forward to the concept of pharmaconutrition where a disease-dedicated nutrition therapy is developed following a rigorous step-by-step procedure. Nutrients are selected according to their pharmacological properties and after an in-depth evaluation of their biological interactions when mixed together. The optimum administration schedule (i.e. dose, route, timing and duration) of the new formulae is then determined in well conducted projective clinical trials where it is administered apart from the standard nutrition to ensure full delivery of the expected doses. SUMMARY: This review suggests moving forward to a pharmaconutrition approach where a rigorous step-by-step procedure would allow overcoming of the difficulties encountered to translate immunonutrition into clinical practice.