Abstract Background Disease management programs (DMPs) for chronic diseases are being increasingly implemented worldwide. Objectives To present a systematic overview of the economic effects of DMPs with Markov models. The quality of the models is assessed, the method by which the DMP intervention is incorporated into the model is examined, and the differences in the structure and data used in the models are considered. Methods A literature search was conducted; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed to ensure systematic selection of the articles. Study characteristics e.g. results, the intensity of the DMP and usual care, model design, time horizon, discount rates, utility measures, and cost-of-illness were extracted from the reviewed studies. Model quality was assessed by two researchers with two different appraisals: one proposed by Philips et al. (Good practice guidelines for decision-analytic modelling in health technology assessment: a review and consolidation of quality asessment. Pharmacoeconomics 2006;24:355-71) and the other proposed by Caro et al. (Questionnaire to assess relevance and credibility of modeling studies for informing health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. Value Health 2014;17:174-82). Results A total of 16 studies (9 on chronic heart disease, 2 on asthma, and 5 on diabetes) met the inclusion criteria. Five studies reported cost savings and 11 studies reported additional costs. In the quality, the overall score of the models ranged from 39% to 65%, it ranged from 34% to 52%. Eleven models integrated effectiveness derived from a clinical trial or a meta-analysis of complete DMPs and only five models combined intervention effects from different sources into a DMP. The main limitations of the models are bad reporting practice and the variation in the selection of input parameters. Conclusions Eleven of the 14 studies reported cost-effectiveness results of less than $30,000 per quality-adjusted life-year and the remaining two studies less than $30,000 per life-year gained. Nevertheless, if the reporting and selection of data problems are addressed, then Markov models should provide more reliable information for decision makers, because understanding under what circumstances a DMP is cost-effective is an important determinant of efficient resource allocation.