Farmers often experience inconsistent responses when using herbicides to terminate an established lucerne pasture prior to cropping. In an attempt to redress this problem, a series of field experiments were conducted between 1999 and 2002 at various locations in southern and northern New South Wales, the Australian Capital Territory, and south Western Australia that aimed to identify management guidelines that improved the efficacy of herbicide mixtures commonly used to remove lucerne. Collectively, these studies indicated that herbicides were generally less effective when applied either early (less than 2 weeks) or late (6 weeks or more) in the regrowth cycle of lucerne after defoliation. Herbicide efficacy tended to be greatest if applied to regrowth 3–5 weeks after defoliation, which corresponds to a time when the lucerne crown and root reserves are likely to be in the process of being replenished by photoassimilates transported from the shoot. The impact of timing of herbicide application in relation to season was compared at a number of locations. Across all the sites and years, spring herbicide applications were generally the most effective, removing on average 87% of the lucerne (range 53–100%) compared with 72% in summer (24–100%) and 60% in autumn (7–92%). Spring applications were also more consistent in their effect, removing >80% of the lucerne plants in 9 out of 12 experiments, whereas similar rates of removal occurred on 4 occasions in 9 summer applications and only twice in 8 autumn applications. Some of the seasonal variation could be explained by differences in the amount of rainfall prior to herbicide applications. It was assumed that the relationship between rainfall and herbicide efficacy reflected the stimulation of lucerne shoot and root growth by the additional soil moisture before herbicide treatment. Herbicide mixtures that contained ingredients such as picloram that retain residual activity in the soil tended to be more effective and were less influenced by lucerne growth and season than those herbicides with little or no residual activity. However, such chemicals could potentially restrict which crops can subsequently be grown after a lucerne pasture has been removed. It was concluded that >80% of lucerne plants were likely to be removed using herbicides provided that the herbicide treatment was applied to actively growing lucerne 3–5 weeks after defoliation, and when greater than 70–95 mm rain had fallen in the 6–8 weeks prior to application.