Several management techniques are effective in controlling Lepidium latifolium (perennial pepperweed) in rangelands and hay meadows; however, this invader’s rapid spread into sensitive aquatic habitats throughout the western US calls for alternative control strategies. To evaluate control methods for use in tidal marshes of San Francisco Estuary, we tested chemical, mechanical, and biological methods in field and greenhouse experiments. In a field experiment in three brackish marshes spanning the estuary, application of the herbicide glyphosate to re-growth of L. latifolium following hand-removal reduced L. latifolium cover by an average of 80% after 2 years and led to a 60% increase in native vegetation cover. Glyphosate alone was less effective at reducing L. latifolium cover (20% decrease) and increasing native cover (34% increase). Preliminary tests of a potential biological control, a native parasitic plant, were not successful, thus plots intended for field trials were instead used to test the newly approved herbicide imazapyr, which showed promise in controlling L. latifolium. An additional greenhouse experiment found large reductions in stem lengths with either glyphosate following clipping or imazapyr with or without clipping, all significantly more so than glyphosate alone. We conclude that an integrated management approach of applying glyphosate following mechanical removal can be effective at reducing L. latifolium cover and allowing recovery of native tidal marsh plants, providing a useful solution for controlling smaller, accessible infestations of the invader. Our preliminary tests of imazapyr suggest that it may be very effective at controlling L. latifolium in tidal marshes, although further assessment of non-target effects and native plant recovery are needed to evaluate its relative merit.