Assisting tobacco farmers to transition to non-tobacco alternatives is a key element of comprehensive tobacco control's end-game strategy and specifically required by the World Health Organization (WHO) Framework Convention for Tobacco Control (FCTC). We examine the historical relationship between tobacco manufacturers and tobacco farmers in the United States, where the duration of the relationship has been longest and use information obtained to inform possible end-game strategies for tobacco control advocates working with tobacco farmers in developing countries. Tobacco Documents obtained under the Master Settlement Agreement (MSA) provide evidence of conflicts between tobacco manufacturers and tobacco farmers. Findings support WHO FCTC articles aimed at helping developing country tobacco farmers adversely affected by tobacco control efforts and highlight difficulties in discouraging tobacco cultivation as long as it remains relatively profitable. We conclude that successful end-game strategies should take a long-term approach aimed at building alliances with tobacco farmers and at creating mechanisms for tobacco farmer investment in local infrastructure.