This paper summarizes a debate on whether meta-analyses and systematic reviews are decisive in formulating guidelines for dietary fat. Held during the 12th congress of the International Society for the Study of Fatty Acids and Lipids in Stellenbosch, South Africa, September 7, 2016, the debate was hosted by the International Union of Nutritional Sciences and the International Expert Movement to Improve Dietary Fat Quality (IEM, www.theiem.org). Clemens von Schacky, Ludwig Maximilians-University, Munich, Germany, supported the statement, describing the types of weaknesses in individual studies and clinical trials. With examples of how to overcome such limitations, he concluded that nutritional guidelines on fat need a proper scientific basis in which randomized controlled trials (RCTs) with clinical endpoints and their meta-analyses are essential and decisive. In contention, Ingeborg Brouwer, Vrije Universiteit, Amsterdam, declared that recommendations on dietary fat intake should always be based on the totality of the evidence, including physiologic and biochemical knowledge and associations from observational epidemiology. RCTs and meta-analyses have their shortcomings, but well-conducted systematic reviews and meta-analyses support a transparent process for developing dietary fat guidelines. Participants agreed that evidence-based decision-making for dietary guidance should consider all the best available evidence using a transparent, systematic review.