The value of glyphosate has been compromised in some fields where weed populations have developed resistance or tolerant species increased. Three case studies related to reduced control from glyphosate are: (1) a weed population that has become resistant to glyphosate, with horseweed in Tennessee as an example; (2) a weed population increases due to lack of control in “glyphosate only” systems, with tropical spiderwort in Georgia cotton used as an example; and (3) the hypothetical resistance of common waterhemp to glyphosate in Illinois. For each of these case studies, an economic analysis was performed using a partial budget approach. This economic analysis provides the cost of control to the farmer when glyphosate fails to control these weeds and gives a critical time in years to compare different glyphosate resistance management philosophies (applicable only before resistance has evolved). The cost of glyphosate-resistant horseweed in cotton-soybean-corn rotation in Western Tennessee was calculated to be $30.46/ha per year. The cost of tropical spiderwort in cotton in southern Georgia was calculated to be $35.07/ha per year. The projected cost if common waterhemp were to develop glyphosate resistance in a corn-soybean rotation in southern Illinois was projected to be $44.25/ha per year, and the critical time was determined to be greater than 20 yr, indicating that a resistance management strategy would extend the value of glyphosate-resistant crops.