The necessity of allocating available, and often scarce, resources to effective interventions 1 has increased awareness of the importance of having a sound evidence base to inform decision-making. For example, the European Union Drug Strategy and Action Plans and regional drug strategies call for the implementation of evidence-based policies 2. These developments present an opportunity for the adoption of evidence-based guidelines such as those mentioned by Davoli et al. 3 and published by the World Health Organization (WHO). In addition, they put pressure on the organizations that disseminate systematic reviews and guidelines to promote knowledge exchange and enable informed decision-making 4. Nevertheless, important obstacles remain to be solved before the Cochrane and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method for developing evidence-based guidelines becomes the gold standard for guidelines in the field of drug addiction. These obstacles pertain to three main dimensions, which will be discussed below: (1) time, (2) consensus and (3) implementation. No matter how fast and adequate is the identification, assessment and synthesis of evidence, it will never catch up with the new demand for knowledge. The time allowed for decision-making, at individual or at political level, is short compared with the time required for accurate systematic reviewing and recommendation development. This is especially true for emerging problems such as new psychoactive substances and new patterns of drug use where, even in the absence of consolidated evidence, decisions need to be taken quickly 5. The handbook of the Cochrane Collaboration 6 states that it generally takes 12 months to conduct a systematic review. If, in practice, this is a theoretical quantity, because systematic reviews require longer efforts, for decision-making this is an incommensurable time (for example, the rotating Presidencies of the Council of the European Union have a 6-month time-span 7). In order to enable informed decision-making, it is necessary to invest in rapid methods to identify and assess the available evidence and to communicate the uncertainties and knowledge gaps. The guidelines development panels ensure consensus among participants by disclosing conflicts of interest, assessing the level of the evidence and determining the strength of the recommendations. These panels are composed of methodologists performing systematic reviewing and clinicians with practical knowledge derived from contact with patients. The first group of professionals assess and synthesize the evidence (and assign the level of confidence in the available evidence) and the second group of professionals endorse the level of evidence. Finally, together they draft the recommendations and determine the strength [3: Table 4]. In order to reach a final agreement on the recommendations, some negotiations take place within the panel. These negotiations are a crucial aspect of the translation of evidence into recommendations for practice. The question is whether or not these negotiations have a rational base. In other words, do the methodologists determine the impact of evidence-informed treatment on real patients? Do the clinicians believe that the statistical inferences from a meta-analysis apply to their patients? Recent research from other fields of knowledge has raised doubts concerning the rationality of decisions by experts 8 that are worth considering. The third critical element in the Cochrane and GRADE methodology for developing guidelines in drug addiction is the implementation aspect. The tables of evidence proposed by the GRADE Working Group to synthesize the results of systematic reviews are extremely complicated and are difficult to apply in practice. Research shows that most guidelines have little impact in practice 9 and, apparently, one of the main obstacles to implementation is lack of clarity. Methods to ensure implementability of guidelines 10 should be incorporated into the development process, ensuring that they do not extend the production time. The Cochrane GRADE method is a step forward for guidelines development in the addiction field, but challenges remain for enabling evidence-informed decision-making. None.