This article reviews, categorizes, and evaluates the objectives, means, and results of the application of material flow analysis (MFA) in waste management. It identifies those areas where MFA methodologies are most successful in supporting waste management decisions. The focus of this review is on the distinction between MFA on the level of goods and on the level of substances. Based on 83 reviewed studies, potentials, strengths, and weaknesses are investigated for the two levels of MFA when applied for analysis, evaluation, and improvement of waste management systems. The differences are discussed in view of effectiveness, applicability, and data availability. The results show that MFA on the level of goods are instrumental for understanding how waste management systems function, facilitating the connections of stakeholders, authorities, and waste management companies. The substance level is essential to assess qualitative aspects regarding resources and environment. Knowledge about the transformation, transport, and storage of valuable and hazardous substances forms the base for identifying both resource potentials and risks for human health and the environment. The results of this review encourage the application of MFA on both levels of goods and substances for decision making in waste management. Because of the mass balance principle, this combination has proven to be a powerful tool for comprehensively assessing if a chosen system reaches designated waste management goals.