Tobacco farming has emerged as an important concern for tobacco control advocates. Tobacco-growing countries face unique and important challenges to comprehensive, intersectoral tobacco control. These challenges stem from narratives that position tobacco as an important driver of economic growth and development, perpetuated by tobacco interests with close ties to government decision-making. While the global tobacco control movement has enshrined a commitment to alternatives to tobacco growing, there remain numerous obstacles. Tobacco growing is often situated in contexts with limited markets for other agricultural products, limited knowledge and economic resources to pursue alternatives, and/or a structure that favours industry control over the supply chain, all constraining the decision space of farmers. An evidence-informed approach is necessary to address tobacco supply, including growing, processing, manufacturing and trade, in this complex context. This paper reviews the economic, environmental and policy context of tobacco growing with an emphasis on the past decade of empirical work on the political economy of tobacco supply and introduces strategies to pursue alternatives. This analysis debunks many of the arguments used to perpetuate the narrative of tobacco’s prosperity and provides critical insights into the institutional constraints faced by government sectors in pursuing a policy of alternatives.