OBJECTIVES: Risk minimization interventions (RMIs) implemented by drug manufacturers aim at optimizing the benefit-risk of medicines when important safety concerns related to product have been identified. In some situations, strict RMIs, such as controlled distribution programs or mandatory certification, may be required. Although aiming to improve patient’s safety, RMIs could be costly, time-consuming, challenging and therefore, generate an undue burden on stakeholders. In some instances, regulatory agencies request that burden of RMIs be evaluated but no methodological guidance is available. The objective of the present study is to identify current methodologies used to evaluate the utility and burden associated with RMIs and to identify methodological gaps. METHODS: A non-systematic literature review was conducted using Medline and Embase in order to identify relevant publications that include an assessment of the utility and/or burden of RMI. Pragmatic searches using Google and Google Scholar search engines completed this analysis. Regulatory agencies websites were also consulted to identify potential existing guidelines related to the evaluation of the burden associated with RMIs.  RESULTS: A total of 362 relevant publications were identified in the literature. Among the methods used, surveys and focus groups appeared to be the most frequent as they allow to gather participants’ opinions providing a better understanding of the burden and potentially identifying optimization opportunities. Mixed-method evaluations were also currently employed as they include several methodologies and usually combine qualitative and quantitative evaluations. Indeed, documenting several aspects of the burden associated with RMI such as costs, time required to comply with specific requirements or healthcare professionals’ opinions is critical to obtain a comprehensive overview of the situation and develop targeted strategies aiming to enhance RMIs implementation and outcomes. CONCLUSIONS: Several methodological gaps have been identified on the methods used to evaluate the utility and burden of RMIs.