With the Millennium Development Goals (MDGs) showing uneven progress, this review identifies possible limitations arising from the MDG framework itself rather than extrinsic issues. A multidisciplinary literature review was conducted with a focus on limitations in the formulation of the MDGs, their structure, content and implementation. Of 1837 MDG-related articles, 90 met criteria for analysis. Articles describe MDGs as being created by only a few stakeholders without adequate involvement by developing countries and overlooking development objectives previously agreed upon. Others claim MDGs are unachievable and simplistic, not adapted to national needs, do not specify accountable parties and reinforce vertical interventions. While MDGs have promoted increased health and well-being in many countries by recognising and deliberating on the possible constraints of the MDG framework, the post-2015 agenda may have even greater impact.