Field and greenhouse studies were conducted in 2007 and 2008 to evaluate the foliar efficacy of saflufenacil on horseweed (Conyza canadensis (L.) Cronq.). In the field, saflufenacil applied alone at the lowest rate (25 g/ha) resulted in less control than all other herbicide treatments that included saflufenacil. The addition of glyphosate to 25 g/ha of saflufenacil increased the level of control over either herbicide applied alone. However, the addition of glyphosate to 50 g/ha of saflufenacil or greater was not beneficial because saflufenacil alone provided at least 95% control. Overall, horseweed height at the time of herbicide application had very little effect on the efficacy of saflufenacil applied alone or in combination with glyphosate. Application variables can enhance the foliar activity of saflufenacil. In the greenhouse, saflufenacil combined with glyphosate provided greater control than saflufenacil applied alone on both glyphosate-susceptible and -resistant horseweed populations. Regardless of horseweed population or glyphosate, saflufenacil had greater activity when crop oil concentrate rather than nonionic surfactant was used as the adjuvant. Decreasing light level within 24 hours of herbicide application resulted in greater saflufenacil activity. Applying saflufenacil in a pH 5 spray solution resulted in greater activity than pH 7 or pH 9. Although effects from saflufenacil applied under different temperatures were evident in early timings, there were no lasting effects on the efficacy of saflufenacil. Saflufenacil had significant activity on both glyphosate-susceptible and -resistant horseweed. Under certain conditions when complete control of horseweed is not achieved, such as low application rates, large target weeds, and varying environmental conditions, application variables including glyphosate tank-mixtures, crop oil concentrate, low spray solution pH, and low light level may increase the level of horseweed control from saflufenacil.